RESUMEN
Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure-activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules' potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.
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Anopheles , Insecticidas , Malaria , Animales , Proteínas Portadoras , Insecticidas/química , Insecticidas/farmacología , Hormonas Juveniles/farmacología , Larva , Simulación del Acoplamiento Molecular , Control de Mosquitos , Mosquitos Vectores , Pirimidinonas/farmacologíaRESUMEN
Fragrance is an integral part of cosmetic products and is often regarded as an overriding factor in the selection of cosmetics among consumers. Fragrances also play a considerable role in masking undesirable smells arising from fatty acids, oils and surfactants that are commonly used in cosmetic formulations. Essential oils are vital assets in the cosmetic industry, as along with imparting pleasant aromas in different products, they are able to act as preservatives and active agents and, simultaneously, offer various benefits to the skin. Moreover, the stimulating demand for natural ingredients has contributed massively to a renewed interest in cosmetic and wellness industries in plant derivatives, especially essential oils. This has led popular cosmetic companies to endorse natural fragrances and opt for minimally processed natural ingredients, given the potentially adverse health risks associated with artificial fragrance chemicals, which are major elements of cosmetics. Among the high-valued essential oils used as fragrances are citrus, lavender, eucalyptus, tea tree and other floral oils, among others, while linalool, geraniol, limonene, citronellol, and citral are much-appreciated fragrance components used in different cosmetics. Thus, this review aimed to highlight the enormous versatility of essential oils as significant sources of natural fragrances in cosmetics and cosmeceuticals. Moreover, a special focus will be laid on the different aspects related to essential oils such as their sources, market demand, chemistry, fragrance classification, aroma profile, authenticity and safety.
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Productos Biológicos/química , Cosmecéuticos/química , Cosméticos/química , Aceites Volátiles/química , Animales , Humanos , Odorantes/análisisRESUMEN
The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a-e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, ß = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.
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Inhibidores de la Ciclooxigenasa 2/química , Indolizinas/química , Antiinflamatorios/química , Cristalografía por Rayos X/métodos , Ciclooxigenasa 2/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Indometacina/química , Relación Estructura-ActividadRESUMEN
Recent mechanistic and epidemiological studies have provided insights into health benefits of dietary lycopene to decrease the risk and complications associated with several chronic diseases such as cardiovascular diseases (CVD), obesity, type 2 diabetes, cancer, and neurodegenerative disorders. These chronic diseases are primarily associated with oxidative stress-induced systemic and low-grade chronic inflammation. Owing to its potent antioxidant properties, lycopene can potentially alleviate enhanced levels of proinflammatory mediators (e.g., proinflammatory cytokines IL-8, -6, and -1, and oxidized phospholipids) and prevent NF-κB activation by modulating oxidative stress. Moreover, lycopene serves as a precursor for various oxidative cleavage products and metabolites including Apo-8'-, apo-10'-, and apo-12'-lycopenals that can interact with multiple transcription factors (e.g., Nrf2, RARs, RXRs, and PPARs) to overexpress antioxidant and cytoprotective Phase II enzymes and other growth-stimulating proteins (e.g., brain-derived neurotrophic factor (BDNF) for enhanced neuroprotection. These events altogether can protect the body from chronic inflammatory disorders. In the present review, the latest mechanistic development from cell and animal models and results of case-control, cohort, and randomized trials are discussed to support the protective part of lycopene in cancer, CVD, and neurodegenerative disorders. This review focuses on cellular and molecular events involved in protective effects of lycopene. Although molecular and cellular mechanisms involved in health-promoting activities of lycopene have been reported, no detailed mechanistic studies have been published. Hence, future studies should be conducted to elucidate the mechanistic role(s) of lycopene-derived oxidation products in modulating cellular signaling.
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Enfermedades Cardiovasculares , Licopeno/uso terapéutico , Neoplasias , Enfermedades Neurodegenerativas , Sustancias Protectoras/uso terapéutico , Tejido Adiposo/metabolismo , Animales , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/prevención & control , Humanos , Hígado/metabolismo , Licopeno/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Neoplasias/epidemiología , Neoplasias/metabolismo , Neoplasias/prevención & control , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/prevención & control , Sustancias Protectoras/farmacologíaRESUMEN
Antiplatelet drugs reduce the risks associated with atherothrombotic events and show various applications in diverse cardiovascular diseases including myocardial infarctions. Efficacy of the current antiplatelet medicines including aspirin, clopidogrel, prasugrel and ticagrelor, and the glycoprotein IIb/IIIa antagonists, are limited due to their increased risks of bleeding, and antiplatelet drug resistance. Hence, it is important to develop new effective antiplatelet drugs, with fewer side-effects. The vast repertoire of natural peptides can be explored towards this goal. Proteins and peptides derived from snake venoms and plants represent exciting candidates for the development of novel and potent antiplatelet agents. Consequently, this review discusses multiple peptides that have displayed antiplatelet aggregation activity in preclinical drug development stages. This review also describes the antiplatelet mechanisms of the peptides, emphasizing the signaling pathways intervened by them. Also, the hurdles encountered during the development of peptides into antiplatelet drugs have been listed. Finally, hitherto unexplored peptides with the potential to prevent platelet aggregation are explored.
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Péptidos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Proteínas/uso terapéutico , Animales , Proteínas en la Dieta/uso terapéutico , Evaluación Preclínica de Medicamentos , Humanos , Péptidos/farmacocinética , Plantas/químicaRESUMEN
BACKGROUND: Many indigenous plants of Mascarene Islands have been used in folkloric medicine to manage diabetes but few species have received scientific attention. Selected traditional medicinal plants (Antidesma madagascariense Lam. -Euphorbiaceae (AM), Erythroxylum macrocarpum O.E.Schulz -Erythroxylaceae (EM), Pittosporum senacia Putterl -Pittosporaceae (PS), Faujasiopsis flexuosa Lam. C.Jeffrey -Asteraceae (FF), Momordica charantia Linn -Cucurbitaceae (MC) and Ocimum tenuiflorum L -Lamiaceae (OT) were evaluated for their antioxidant, antiglycation and cytotoxic potential in vitro. METHODS: Graded concentrations (1.25-100 µg/mL) of the crude methanolic and water extracts and fractions (dichloromethane, ethyl-acetate, n-butanol and water) were evaluated for abilities to scavenge 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH), nitric oxide (NO), superoxide (SO) radicals and to inhibit lipoxygenase and formation of advanced glycation endproduct (AGE) in vitro. The MTT (3-(4, 5-dimethylthazol-2-yl)-2,5-diphenyl tetrazonium bromide) cytotoxicity test was performed on 3T3 cell line. RESULTS: Only IC50 for DPPH, SO, NO and lipoxygenase for AM, FF and OT crude extracts and fractions were comparable to ascorbic acid and quercetin activity. Crude aqueous extracts of AM and FF showed IC50 of 4.08 and 3.89 µg/mL respectively for lipoxygenase which was significantly lower (p < 0.05) than quercetin (10.86 ± 0.68 µg/mL). The three crude aqueous extracts of these plants and their n-butanol fractions also showed antiglycation activities (p < 0.05) comparable to aminoguanidine. Increasing concentrations (250-2000 µg/mL) of the six crude extracts (Methanol and water) and their fractions did not inhibit mitochondrial respiration as measured by MTT cytotoxicity assay. CONCLUSION: AM, FF and OT crude extracts and fractions have potent antioxidant and antiglycation properties with no apparent cytotoxicity and might have prophylactic and therapeutic potentials in the management of diabetes and related complications. Our study tends to validate the traditional use of these medicinal herbs and food plants as complementary and alternative medicines.
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Antioxidantes/farmacología , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Lipooxigenasa/metabolismo , Magnoliopsida , Extractos Vegetales/farmacología , Plantas Medicinales , Células 3T3 , Animales , Asteraceae , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Inhibidores Enzimáticos/farmacología , Euphorbiaceae , Islas , Magnoliopsida/toxicidad , Ratones , Mitocondrias/efectos de los fármacos , Ocimum , Fitoterapia , Extractos Vegetales/toxicidad , Plantas Medicinales/toxicidadRESUMEN
Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research.
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Fármacos Antiobesidad/farmacología , Plantas/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Depresores del Apetito/farmacología , Humanos , MetabolómicaRESUMEN
Suaeda fruticosa is an edible medicinal halophyte known for its traditional uses. In this study, methanol and dichloromethane extracts of S. fruticosa were explored for phytochemical, biological and toxicological parameters. Total phenolic and flavonoid constituents were determined by using standard aluminum chloride and Folin-Ciocalteu methods, and UHPLC-MS analysis of methanol extract was performed for tentative identification of secondary metabolites. Different standard methods like DPPH, ABTS, FRAP, CUPRAC, total antioxidant capacity (TAC), and metal chelation assays were utilized to find out the antioxidant potential of extracts. Enzyme inhibition studies of extracts against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase and, α-glucosidase enzymes were also studied. Likewise, the cytotoxicity was also assessed against MCF-7, MDA-MB-231, and DU-145 cell lines. The higher phenolic and flavonoids contents were observed in methanol extracts which can be correlated to its higher radical scavenging potential. Similarly, 11 different secondary metabolites were tentatively identified by UHPLC profiling. Both the extract showed significant inhibition against all the enzymes except for α-glucosidase. Moreover, docking studies were also performed against the tested enzymes. In the case of cytotoxicity, both the samples were found moderately toxic against the tested cell lines. This plant can be explored further for its potential therapeutic and edible uses.
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Antineoplásicos/farmacología , Antioxidantes/farmacología , Chenopodiaceae/química , Inhibidores Enzimáticos/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Línea Celular Tumoral , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Enzimas/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Fitoquímicos/química , Fitoquímicos/metabolismo , Extractos Vegetales/química , Plantas Medicinales/química , Unión ProteicaRESUMEN
This study sets out to probe into total bioactive contents, UHPLC-MS secondary metabolites profiling, antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating) and enzyme inhibitory (acetylcholinesterase- AChE, butyrylcholinesterase- BChE, α-amylase, α glucosidase, and tyrosinase) activities of methanol extract of Aerva javanica, also known as desert cotton or Kapok bush. Aerva javanica contains considerable phenolic (44.79 ± 3.12 mg GAE/g) and flavonoid (28.86 ± 0.12 mg QE/g) contents which tends to correlate with its significant antioxidant potential for ABTS, FRAP and CUPRAC assays with values of 101.41 ± 1.18, 124.10 ± 1.71 and 190.22 ± 5.70 mg TE/g, respectively. The UHPLC-MS analysis identified the presence of 45 phytochemicals belonging to six major groups: phenolic, flavonoids, lignin, terpenes, glycoside and alkaloid. Moreover, the plant extract also showed potent inhibitory action against AChE (3.73 ± 0.22 mg GALAE/g), BChE (3.31 ± 0.19 mg GALAE/g) and tyrosinase (126.05 ± 1.77 mg KAE/g). The observed results suggest A. javanica could be further explored as a natural source of bioactive compounds.
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Amaranthaceae/química , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Fitoquímicos/análisis , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Flavonoides/análisis , Inhibidores de Glicósido Hidrolasas/farmacología , Metanol/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Fenoles/análisis , Fitoquímicos/farmacología , Extractos Vegetales/química , Metabolismo Secundario , alfa-Amilasas/antagonistas & inhibidores , alfa-Glucosidasas/metabolismoRESUMEN
Neurodegenerative disorders are estimated to become the second leading cause of death worldwide by 2040. Despite the widespread use of diverse allopathic drugs, these brain-associated disorders can only be partially addressed and long term treatment is often linked with dependency and other unwanted side effects. Nature, believed to be an arsenal of remedies for any illness, presents an interesting avenue for the development of novel neuroprotective agents. Interestingly, inhibition of cholinesterases, involved in the breakdown of acetylcholine in the synaptic cleft, has been proposed to be neuroprotective. This review therefore aims to provide additional insight via docking studies of previously studied compounds that have shown potent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. Indeed, the determination of potent plant-based ligands for this purpose through in silico methods enables the elimination of lengthy and costly traditional methods of drug discovery. Herein, a literature search was conducted to identify active phytochemicals which are cholinesterase inhibitors. Following which in silico docking methods were applied to obtain docking scores. Compound structures were extracted from online ZINC database and optimized using AM1 implemented in gaussian09 software. Noteworthy ligands against AChE highlighted in this study include: 19,20-dihydroervahanine A and 19, 20-dihydrotabernamine. Regarding BChE inhibition, the best ligands were found to be 8-Clavandurylkaempferol, Na-methylepipachysamine D; ebeiedinone; and dictyophlebine. Thus, ligand optimization between such phytochemicals and cholinesterases coupled with in vitro, in vivo studies and randomized clinical trials can lead to the development of novel drugs against neurodegenerative disorders.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Acetilcolinesterasa , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Colinesterasas , Humanos , Simulación del Acoplamiento Molecular , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fitoquímicos/farmacología , Relación Estructura-ActividadRESUMEN
Calligonum polygonoides L. also known as famine food plant, is normally consumed in times of food scarcity in India and Pakistan and also used traditionally in the management of common diseases. The present design aims to provide an insight into the medicinal potential of four solvent extracts of C. polygonoides via an assessment of its phytochemical profile, antioxidant and enzyme inhibitory potential. Phytochemical composition was estimated by deducing total bioactive constituents, UHPLC-MS secondary metabolites profile, and HPLC phenolic quantification. Antioxidant potential was determined via six methods (radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum total antioxidant capacity and metal chelation activity). Enzyme inhibitory potential was assessed against clinical enzymes (acetylcholinesterase -AChE, butyrylcholinesterase -BChE, tyrosinase, and α-amylase). The highest amounts of phenolic contents were found in chloroform extract (76.59 mg GAE/g extract) which may be attributed to its higher radical scavenging, reducing power and tyrosinase inhibition potential. The n-butanol extract containing the maximum amount of flavonoids (55.84 mg RE/g extract) exhibited highest metal chelating capacity. Similarly, the n-hexane extract was found to be most active against AChE (4.65 mg GALAE/g extract), BChE (6.59 mg GALAE/g extract), and α-amylase (0.70 mmol ACAE/g extract) enzymes. Secondary metabolite assessment of the crude methanol extract as determined by UHPLC-MS analysis revealed the presence of 24 (negative ionization mode) and 15 (positive ionization mode) secondary metabolites, with most of them belonging to phenolic, flavonoids, terpene, and alkaloid groups. Moreover, gallic acid and naringenin were the main phenolics quantified by HPLC-PDA analysis in all the tested extracts (except n-butanol extract). PCA statistical analysis was also conducted to establish any possible relationship amongst bioactive contents and biological activities. Overall, the C. polygonoides extracts could be further considered to isolate bioactive enzyme inhibitory and antioxidant natural phytocompounds.
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Hambruna , Extractos Vegetales , India , Análisis Multivariante , Pakistán , Fitoquímicos/análisis , Plantas ComestiblesRESUMEN
In this study, different parts (aerial, stem and root) of Salvadora oleoides Decne were investigated in order to explore their phytochemical composition and biological potential. The bioactive contents were evaluated by conventional spectrophotometric methods. Additionally, the secondary metabolite compounds were identified by UHPLC-MS analysis. Biological potential was evaluated by determining antioxidant (DPPH, FRAP, and Phosphomolybdenum) and enzyme inhibitory (butrylcholinesterase and lipoxygenase) effects. Higher total bioactive contents were found in methanolic extracts which tend to correlate with higher radical scavenging and reducing potential of these extracts. LC/MS spectrum revealed the presence of 16 different secondary metabolites belonging to terpene, glucoside and sesquiterpenoid dervivatives. Glucocleomin and emotin A were the main compounds present in all three parts. The strongest butrylcholinesterase and lipoxygenase inhibitory activity was observed for root and stem DCM extracts. Demonstrated biological potential of S. oleoides plant can trace a new road map for developing newly designed bioactive pharmaceuticals.
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Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Componentes Aéreos de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Salvadoraceae/metabolismo , Antioxidantes/química , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Metanol/química , Fitoquímicos/análisis , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Raíces de Plantas/química , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Salvadoraceae/química , Metabolismo Secundario , Sesquiterpenos/análisis , Sesquiterpenos/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rodrigues, is an autonomous island that forms part of the Republic of Mauritius. It is a component of the Mascarene archipelago alongside Mauritius and Reunion island. Despite their relative geographical proximity, each island has its own unique biodiversity and indigenous knowledge. Nonetheless, there is no documentation of the use of animal-based remedies (ABR) in Rodrigues. This study was therefore designed to gather and compare primary traditional knowledge on the different ABR used by Rodriguans. AIM OF THE STUDY: To collect, analyse, document, compare, and disseminate the use of ABR against common human ailments in Rodrigues island. METHODS: Data was collected following interviews from key informants (nâ¯=â¯150). Primary data collected in the present study was compared with those reported from the nearest island, Mauritius. Three quantitative indices including (i) the frequency of citation, (ii) the similarity ratio and the percentage of shared uses among the two islands and (iii) new uses and percentage of new uses recorded in Rodrigues for each animal species mentioned were calculated. RESULTS: A total of 32 animal species belonging to 13 taxonomic groups among which 55% were vertebrates and 45% invertebrates were reported to treat 38 different ailment conditions. Altogether, 73 distinct medicinal preparations employing 22 different animal parts and by-products were concocted from the different animal species reported. Most used animal parts were meat (21%) followed by the whole body (14%). The preparations were either administered orally (78%) or topically (22%). Interestingly, resources such as the Rodriguan bat (Pteropus rodricensis) and honey are unique to the island and have never been studied before. Pteropus rodricensis is an endangered species while Carcharodon carcharias is a vulnerable one. The shared medicinal uses of the species among the 2 islands ranged from 0 to 50% with the most similar uses (50%) being for Columba livia and Donax Spp. respectively. The proportion of new uses of animal species recorded in Rodrigues was higher (NURâ¯≥â¯30%) for Panulirus penicillatus, Ovis aries, Gallus gallus domesticus, Scutigera coleoptrata, Apis mellifera, Bos taurus and Capra aegagrus hircus. CONCLUSION: Rodriguans were found to possess valuable knowledge on a plethora of ABR. It is believed that the present documentation will serve to record and present this vanishing knowledge to the scientific community before it is further eroded from the island. Given the dearth of primary published information on zootherapeutic practices in Rodrigues, this study opens new avenues for biomedicine development in an attempt to develop alternative therapies or complement existing ones.
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Conocimientos, Actitudes y Práctica en Salud , Medicina Tradicional , Adulto , Animales , Etnofarmacología , Femenino , Humanos , Masculino , Mauricio , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The current research work was conducted in order to probe into the biochemical and toxicological characterisation of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (Choisy.) aerial parts. Biological fingerprints were assessed for in vitro antioxidant, key enzyme inhibitory and cytotoxicity potential. Total bioactive contents were determined spectrophotometrically and the secondary metabolite components of methanol extract was assessed by UHPLC mass spectrometric analysis. The antioxidant capabilities were evaluated via six different in vitro antioxidant assays namely DPPH, ABTS (free radical scavenging), FRAP, CUPRAC (reducing antioxidant power), phosphomolybdenum (total antioxidant capacity) and ferrous chelating activity. Inhibition potential against key enzymes urease, α-glucosidase and cholinesterases were also determined. Methanol extract exhibited higher phenolic (24.01 mg GAE/g extract) as well as flavonoid (41.51â¯mg QE/g extract) contents. Phytochemical profiling of methanol extract identified a total of twenty secondary metabolites and the major compounds belonged to flavonoids, phenolics and alkaloid derivatives. The findings of antioxidant assays revealed the methanol extract to exhibit stronger antioxidant (except phosphomolybdenum) activities. Similarly, the methanol extract showed highest butyrylcholinesterase and urease inhibition. The DCM extract was most active for phosphomolybdenum and α-glucosidase inhibition assays. Moreover, both extracts exhibited significant cytotoxic potential against five (MCF-7, MDA-MB-231, CaSki, DU-145, and SW-480) human carcinoma cell lines with half maximal inhibitory concentration values of 22.09 to 257.2 µg/mL. Results from the present study highlighted the potential of B. glabra aerial extracts to be further explored in an endeavour to discover novel phytotherapeutics as well as functional ingredients.
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Nyctaginaceae/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Antioxidantes/química , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/química , Inhibidores de Glicósido Hidrolasas/química , Humanos , Células MCF-7 , Metanol/química , Fenoles/química , Fitoquímicos/química , alfa-Glucosidasas/químicaRESUMEN
Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune diseases and put into the limelight of the scientific community several health-promoting effects of flavonoids which could be beneficial for the development of novel drugs from natural products. Despite available reviews on flavonoids targeting various disease conditions, a comprehensive review of flavonoids for autoimmune diseases is still lacking. To the best of our knowledge, this is the first attempt to review the potential of flavonoids for autoimmune diseases. The structure-activity relationship of flavonoids in this review revealed that the rearrangement and introduction of other functional groups into the basic skeleton of flavonoids might lead to the development of new drugs which will be helpful in relieving the painful symptoms of various autoimmune diseases.
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Antiinflamatorios/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Flavonoides/uso terapéutico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Antiinflamatorios/toxicidad , Enfermedades Autoinmunes/genética , Flavonoides/química , Flavonoides/farmacocinética , Flavonoides/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Relación Estructura-ActividadRESUMEN
Tragopogon dubius and Tussilago farfara are consumed as vegetables and used in folk medicine to manage common diseases. Herein, the chemical compositions and biological activities of different leaf extracts (ethyl acetate, methanol, and water) of T. dubius and T. farfara were evaluated. The antibacterial, antifungal, and antioxidant abilities of the extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating assays. Enzyme inhibitory potentials were evaluated against cholinesterases, tyrosinase, α-amylase and α-glucosidase. Complexes of bioactive compounds (chlorogenic and rosmarinic acid) were docked into the enzymatic cavity of α-glucosidase and subjected to molecular dynamic calculation, enzyme conformational stability, and flexibility analysis. T. dubius and T. farfara extracts showed remarkable antioxidant potentials. Ethyl acetate extracts of T. dubius and T. farfara were the most potent inhibitors of acetylcholinesterase and butyrylcholinesterase. T. dubius ethyl acetate extract and T. farfara methanolic extract showed noteworthy activity against α-glucosidase. High performance liquid chromatography analysis revealed the abundance of some phenolic compounds including chlorogenic and rosmarinic acids. Ethyl acetate extract of T. dubius showed notable antifungal activity against all strains. Docking studies showed best pose for chlorogenic acid was stabilized by a network of hydrogen bonds with residues Asp1157, Asp1279, whereas rosmarinic acid showed several hydrogen bonds with Asp1157, Asp1420, Asp1526, Lys1460 and Trp1369. This study further validates the use of T. dubius and T. farfara in traditional medicine, as well as act as a stimulus for further studies for future biomedicine development. Communicated by Ramaswamy H. Sarma.
Asunto(s)
Asteraceae/química , Tragopogon/química , Tussilago/química , Acetilcolinesterasa/metabolismo , Antioxidantes/química , Butirilcolinesterasa/metabolismo , Cinamatos/farmacología , Depsidos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Flavonoides/sangre , Flavonoides/farmacología , Simulación del Acoplamiento Molecular/métodos , Monofenol Monooxigenasa/metabolismo , Fenoles/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , alfa-Amilasas/metabolismo , alfa-Glucosidasas/metabolismo , Ácido RosmarínicoRESUMEN
The phytochemical composition of different extracts obtained from stinking chamomile (Anthemis cotula L.) was investigated. Ethanol was used as solvent and accelerated solvent extraction (ASE), microwave assisted extraction (MAE), maceration, soxhlet extraction (SE), and ultrasound assisted extraction (UAE) were applied on plant material. Comparison of the phytochemical contents, antioxidant, and enzyme inhibitory properties were performed. The most abundant sesquiterpene in the extracts was anthecotuloide, while the most present phenolics were caffeoyl quinic acid, quercetin, and kaempferol derivatives. UAE extract was the most efficient in the extraction of sesquiterpenoids and polyphenols. Considering the assays on antioxidant activity and enzyme inhibition, ASE extract showed highest phenolic content (62.92 mg gallic acid equivalent/g extract). Likewise, this extract showed highest radical scavenging (103.44 mg trolox equivalent [TE]/g extract and 155.70 mg TE/g extract, for DPPH and ABTS assays respectively) and reducing power potential (435.32 and 317.89 mg TE/g extract, for CUPRAC and FRAP assays, respectively). The different extracts showed similar results in the enzyme inhibition assays suggesting that the extraction methods used have no effect on observed enzyme activities. Novelty of our findings are the inhibitory action of the ethanol extract of A. cotula aerial parts on key enzymes associated with Alzheimer's disease (acetyl cholinesterase, butyryl cholinesterase), type 2 diabetes (α-amylase, α-glucosidase), and skin hyperpigmentation disorders (tyrosinase). Data collected from the present work further appraises the multiple potential biological properties of stinking chamomile suggesting the need for further investigation on its constituents.
Asunto(s)
Anthemis/química , Fraccionamiento Químico/métodos , Extractos Vegetales/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Inhibidores Enzimáticos/análisis , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/análisis , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Lactonas/análisis , Lactonas/aislamiento & purificación , Microondas , Componentes Aéreos de las Plantas/química , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Polifenoles/análisis , Polifenoles/aislamiento & purificación , Sesquiterpenos/análisis , Sesquiterpenos/aislamiento & purificación , Solventes/química , Ondas UltrasónicasRESUMEN
BACKGROUND: Benzothiazole derivatives are known for anti-TB properties. Based on the known anti-TB benzothiazole pharmacophore, in the present study, we described the synthesis, structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives (BNTZ 1-7 and BNTZ 8-13). OBJECTIVE: The study aims to carry out the development of benzothiazole based anti-TB compounds. METHODS: Title compounds are synthesized by microwave method and purified by column chromatography. Characterization of the compounds is achieved by FT-IR, NMR (1H and 13C), LCMS and elemental analysis. Screening of test compounds for anti-TB activity is achieved by Resazurin Microplate Assay (REMA) Plate method. RESULTS: It was noted that the BNTZ compound with an isoquinoline nucleus (BNTZ 9) exhibited remarkable anti-tubercular activity at 8 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of Mycobacterium tuberculosis. On the other hand, the BNTZ compound with a naphthalene nucleus (BNTZ 2) revealed anti-tubercular activity at 6 µg/mL and 11 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of M. tuberculosis, respectively. One of the selected BNTZ derivatives BNTZ 13 was used for single crystal X-ray studies. CONCLUSION: To identify the appropriate target for potent BNTZ compounds from the series, molecular modeling studies revealed the multiple strong binding of several BNTZs with mycobacterium lysine-É-aminotransferase and decaprenyl-phosphoryl-ß-D-ribose 2'-oxidase. The interaction is derived by forming favorable hydrogen bonds and stacking interactions. This new class of BNTZ compounds gave promising anti-tubercular actions in the low micromolar range, and can be further optimized on a structural basis to develop promising, novel, BNTZ pharmacophore-based anti-tubercular drugs.
Asunto(s)
Antituberculosos/química , Antituberculosos/farmacología , Benzotiazoles/química , Benzotiazoles/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Antituberculosos/síntesis química , Benzotiazoles/síntesis química , Cromatografía Liquida , Simulación por Computador , Cristalografía por Rayos X , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Análisis Espectral/métodos , Relación Estructura-ActividadRESUMEN
Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay. In silico molecular-docking study was conducted for compounds 5a-j against enoyl-[acyl-carrier] protein reductase, a key enzyme of the type II fatty acid synthesis that has attracted much interest for the development of novel anti-TB compounds. Thereafter, molecular dynamic (MD) simulation was undertaken for the most active inhibitors. Compounds 5i and 5j with the methoxy functional group at the meta position of the benzoyl group, which was at the third position of the indolizine nucleus, demonstrated encouraging anti-TB activity against MDR strains of MTB at 16 µg/mL. In silico studies showed binding affinity within the range of 7.07-8.57 kcal/mol, with 5i showing the highest binding affinity. Hydrogen bonding, π-π- interactions, and electrostatic interactions were common with the active site. Most of these interactions occurred with the catalytic amino acids (Pro193, Tyr158, Phe149, and Lys165). MD simulation showed that 5j possessed the highest binding affinity toward the enzyme, according to the two calculation methods (MM/PBSA and MM/GBSA). The single-crystal X-ray studies of compounds 5c and 5d revealed that the molecular arrangements in these two structures were mostly guided by C-H···O hydrogen-bonded dimeric motifs and C-H···N hydrogen bonds, while various secondary interactions (such as π···π and C-H···F) also contributed to crystal formation. Compounds 5a, 5c, 5i, and 5j exhibited no toxicity up to 500 µg/mL. In conclusion, 5i and 5j are promising anti-TB compounds that have shown high affinity based on docking and MD simulation results.
Asunto(s)
Antituberculosos , Proteínas Bacterianas , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Indolizinas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mycobacterium tuberculosis/crecimiento & desarrollo , Antituberculosos/síntesis química , Antituberculosos/química , Antituberculosos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Humanos , Indolizinas/síntesis química , Indolizinas/química , Indolizinas/farmacología , Leucocitos Mononucleares/metabolismoRESUMEN
Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB). Many compounds exhibited significant inhibitory activity against MTB H37Rv strains. Indolizines 2d, 2e, and 4 were also found to be active against MTB clinical isolates with multi-resistance to rifampicin and isoniazid. Indolizine 4 was identified as the most promising anti-mycobacterial agent, displaying minimum inhibitory concentration (MIC) values of 4 and 32 µg/mL against H37Rv and MDR strains, respectively. Furthermore, an in silico study was carried out for prospective molecular target identification and revealed favorable interactions with the target enzymes CYP 121, malate synthase, and DNA GyrB ATPase. None of the potent molecules presented toxicity against peripheral blood mononuclear (PBM) cell lines, demonstrating their potentiality to be used for drug-sensitive and drug-resistant tuberculosis therapy.