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1.
Molecules ; 29(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792255

RESUMO

The rapid advancements in nanotechnology in the field of nanomedicine have the potential to significantly enhance therapeutic strategies for cancer treatment. There is considerable promise for enhancing the efficacy of cancer therapy through the manufacture of innovative nanocomposite materials. Metallic nanoparticles have been found to enhance the release of anticancer medications that are loaded onto them, resulting in a sustained release, hence reducing the dosage required for drug administration and preventing their buildup in healthy cells. The combination of nanotechnology with biocompatible materials offers new prospects for the development of advanced therapies that exhibit enhanced selectivity, reduced adverse effects, and improved patient outcomes. Chitosan (CS), a polysaccharide possessing distinct physicochemical properties, exhibits favorable attributes for controlled drug delivery due to its biocompatibility and biodegradability. Chitosan nanocomposites exhibit heightened stability, improved biocompatibility, and prolonged release characteristics for anticancer medicines. The incorporation of gold (Au) nanoparticles into the chitosan nanocomposite results in the manifestation of photothermal characteristics, whereas the inclusion of silver (Ag) nanoparticles boosts the antibacterial capabilities of the synthesized nanocomposite. The objective of this review is to investigate the recent progress in the utilization of Ag and Au nanoparticles, or a combination thereof, within a chitosan matrix or its modified derivatives for the purpose of anticancer drug delivery. The research findings for the potential of a chitosan nanocomposite to deliver various anticancer drugs, such as doxorubicin, 5-Fluroacil, curcumin, paclitaxel, and 6-mercaptopurine, were investigated. Moreover, various modifications carried out on the chitosan matrix phase and the nanocomposite surfaces to enhance targeting selectivity, loading efficiency, and pH sensitivity were highlighted. In addition, challenges and perspectives that could motivate further research related to the applications of chitosan nanocomposites in cancer therapy were summarized.


Assuntos
Antineoplásicos , Quitosana , Ouro , Nanopartículas Metálicas , Nanocompostos , Prata , Quitosana/química , Nanocompostos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Prata/química , Humanos , Nanopartículas Metálicas/química , Ouro/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico , Animais
2.
Viruses ; 16(5)2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38793638

RESUMO

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise the effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, the mechanism of infection, the role of angiotensin-converting enzyme 2, the host defence responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Mutação , SARS-CoV-2 , Desenvolvimento de Vacinas , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia
3.
J Pharm Pharmacol ; 76(1): 13-22, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38007394

RESUMO

OBJECTIVES: The co-occurrence of melanoma and Parkinson's disease (PD) is higher than expected. We review the relationship between melanoma and PD, then proffer a hypothesis of how dysregulated human tyrosinase could be involved in both diseases via the loss of dopamine and neuromelanin-positive neurons in PD and the genesis alterations in melanin content during melanoma. KEY FINDINGS: There are a surprising number of links between skin disorders and neurodegenerative diseases. Some risk factors related to the co-occurrence of PD and melanoma have been extensively investigated over the past 15 years. It has been proposed that human tyrosinase, an enzyme participating in the biosynthesis of neuromelanin in the brain and of melanin in the skin, plays a role. Abnormally dysregulated human tyrosinase impacts the genesis and progression of melanoma and PD. SUMMARY: The dual role of human tyrosinase places it as the potential critical link between these seemingly distinct conditions. Detecting and monitoring human tyrosinase activity in the progression of melanoma and PD opens new opportunities for early diagnosis and treatment of both diseases.


Assuntos
Melanoma , Doença de Parkinson , Humanos , Monofenol Mono-Oxigenase , Melaninas , Pele
4.
Molecules ; 28(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37894513

RESUMO

Developing a variety of safe and effective functioning wound dressings is a never-ending objective. Due to their exceptional antibacterial activity, biocompatibility, biodegradability, and healing-promoting properties, functionalized chitosan nanocomposites have attracted considerable attention in wound dressing applications. Herein, a novel bio-nanocomposite membrane with a variety of bio-characteristics was created through the incorporation of zinc oxide nanoparticles (ZnONPs) into amine-functionalized chitosan membrane (Am-CS). The developed ZnO@Am-CS bio-nanocomposite membrane was characterized by various analysis tools. Compared to pristine Am-CS, the developed ZnO@Am-CS membrane revealed higher water uptake and adequate mechanical properties. Moreover, increasing the ZnONP content from 0.025 to 0.1% had a positive impact on antibacterial activity against Gram-positive and Gram-negative bacteria. A maximum inhibition of 89.4% was recorded against Escherichia coli, with a maximum inhibition zone of 38 ± 0.17 mm, and was achieved by the ZnO (0.1%)@Am-CS membrane compared to 72.5% and 28 ± 0.23 mm achieved by the native Am-CS membrane. Furthermore, the bio-nanocomposite membrane demonstrated acceptable antioxidant activity, with a maximum radical scavenging value of 46%. In addition, the bio-nanocomposite membrane showed better biocompatibility and reliable biodegradability, while the cytotoxicity assessment emphasized its safety towards normal cells, with the cell viability reaching 95.7%, suggesting its potential use for advanced wound dressing applications.


Assuntos
Quitosana , Nanocompostos , Óxido de Zinco , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas
5.
Foods ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36673446

RESUMO

Four tannin samples extracted from chestnut wood (tannin oenologique, TO), grape (tannin VR grape, TVG), oak gall (tannin galalcool, TG), and oak tree (tannin VR supra elegance, TE) were evaluated for antioxidant and antibacterial activity. The highest total phenolic content (TPC) values were observed in the order of TVG > TG > TE > TO (p < 0.05). The antioxidant activities of all samples were determined in terms of DPPH radical scavenging activity, reducing power, metal-chelating activity, and linoleic acid peroxidation assay. The antioxidant activities of all samples vary and no correlation was observed with the respective TPC values of each sample. Antibacterial activities indicate that all samples showed more or less inhibitory effects against selected Gram-positive and Gram-negative bacteria. Based on antioxidant and antibacterial activity, TO and TVG were selected for the beef mince quality preservation study during refrigerated storage. Both TO and TVG at two different concentrations, 0.25 and 0.5%, could cease the chemical and microbial changes as compared to the control sample. Although total viable count (TVC) did not show a significant difference, the H2S-producing bacteria count was lower in all samples treated with TO and TVG compared to sodium metabisulfite (SMS) and the control sample (p < 0.05). Therefore, TO and TVG could be promising natural food preservatives during refrigerated storage.

6.
Sci Transl Med ; 14(662): eabj2381, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103517

RESUMO

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureus and Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90 ≤ 0.06 µg/ml) against hundreds of isolates of methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficile infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.


Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Positivas , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Biofilmes , Glicopeptídeos/farmacologia , Glicopeptídeos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Mamíferos , Camundongos , Testes de Sensibilidade Microbiana , Streptococcus pneumoniae , Vancomicina/farmacologia , Vancomicina/uso terapêutico
7.
Molecules ; 27(11)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35684571

RESUMO

It is beyond doubt that short peptides hold significant promise in bio-medicine, as the most versatile molecules, both structurally and functionally [...].


Assuntos
Medicina , Peptídeos , Peptídeos/química
8.
Pharmaceutics ; 14(5)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35631572

RESUMO

This study aimed to develop synergistic therapies to treat superbug infections through the encapsulation of sortase A inhibitors (SrtAIs; trans-chalcone (TC), curcumin (CUR), quercetin (QC), or berberine chloride (BR)) into MCM-41 mesoporous silica nanoparticles (MSNs) or a phosphonate-modified analogue (MCM-41-PO3-) to overcome their poor aqueous solubility. A resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading antimicrobial peptides (AMPs; pexiganan (PEX), indolicidin (INDO), and [I5, R8] mastoparan (MASTO)), were determined against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results demonstrated that the MCM-41 and MCM-41-PO3- formulations significantly improved the aqueous solubility of each SrtAI. The MICs for SrtAI/MCM-41-PO3- formulations were lower compared to the SrtAI/MCM-41 formulations against tested bacterial strains, except for the cases of BR/MCM-41 and QC/MCM-41 against P. aeruginosa. Furthermore, the following combinations demonstrated synergy: PEX with TC/MCM-41 (against all strains) or TC/MCM-41-PO3- (against all strains except P. aeruginosa); PEX with BR/MCM-41 or BR/MCM-41-PO3- (against MSSA and MRSA); INDO with QC/MCM-41 or QC/MCM-41-PO3- (against MRSA); and MASTO with CUR/MCM-41 (against E. coli). These combinations also reduced each components' toxicity against human embryonic kidney cells. In conclusion, MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.

9.
J Ethnopharmacol ; 295: 115314, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35490899

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus (Thunb.) belongs to the ground family, Cucurbitaceae, known for edible fruit. Besides nutritional benefits, the traditional herbal practitioners in Pakistan and India used their seeds to treat gastrointestinal, respiratory, and urinary disorders. In Northern Sudan, its seeds are often used as a laxative. Its root is laxative and emetic at a high dose. Its seeds are also used to treat bedwetting and urinary tract obstruction. AIM OF THE STUDY: This study aimed to elucidate the multi-target mechanisms of Citrullus lanatus seeds to treat asthma and diarrhea. The pharmacological experiments were designed and conducted, along with the pharmacology network and molecular docking predictions, to verify the seeds biopotency for antispasmodic and bronchodilator properties. METHODS: LC ESI-MS/MS were performed to identify the potentially active compounds in hydroethanolic extract of Citrullus lanatus seeds, then to quantify them by HPLC. The quantified bioactive compounds of Citrullus lanatus, i.e., stigmasterol, quinic acid, malic acid, epicatechin, caffeic acid, rutin, p-coumaric acid, quercetin, ferulic acid, scopoletin, apigenin, and kaempferol were subjected to in silico studies for molecular docking. The hydroethanolic extract of Citrullus lanatus seeds was examined on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. RESULTS: In silico studies revealed that bioactive compounds of C. lanatus seeds interfere with asthma and diarrhea-associated target genes, which are a member of calcium mediate signaling, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercetin, kaempferol, and scopoletin were stronger binding to voltage-gated calcium channels, calcium/calmodulin-dependent protein kinase, myosin light chain kinase, and phosphoinositide phospholipase C, thus, exerting calcium channel blocker activity. The hydroethanolic extract of C. lanatus seeds exerted a concentration-dependent relaxant response for the spasmolytic response on isolated jejunum and trachea preparations and caused relaxation of spastic contraction of K+ (80 mM). Furthermore, it caused a non-parallel rightward shift with suppression of calcium concentration-response curves. In animal models, the Cl.EtOH showed antiperistalsis, antidiarrheal and antisecretory response. CONCLUSION: Thus, we confirm Citrullus lanatus seeds have some medicinal effects by regulating the contractile response through target proteins of calcium mediates signaling and can be a promising component in the medical treatment for asthma and diarrhea.


Assuntos
Asma , Citrullus , Animais , Antidiarreicos/química , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Asma/tratamento farmacológico , Cálcio , Citrullus/química , Diarreia/tratamento farmacológico , Etanol/uso terapêutico , Quempferóis/uso terapêutico , Laxantes/uso terapêutico , Simulação de Acoplamento Molecular , Paquistão , Parassimpatolíticos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Quercetina/uso terapêutico , Coelhos , Rutina , Escopoletina , Sementes/química , Espectrometria de Massas em Tandem
10.
Biomed Res Int ; 2022: 2277417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386306

RESUMO

The study was an extension of our earlier work on antiinflammatory and anticancer properties of G. asiatica fruit. We aimed to develop a bioassay guided multistep purification technique for producing bioactive fractions of G. asiatica crude extracts. Dried fruit powder was sequentially fractionated with 100% dichloromethane, 100% methanol (MeOH), and 50% MeOH. Active extracts were subjected to liquid-liquid partitioning followed by subfractionation using RP-HPLC. Antioxidant, antiinflammatory, and anticancer activities of the fruit extracts, and their potent fractions were evaluated in vitro, while identification of compounds from the bioactive fractions was performed by ESI-MS/MS analysis. The amount of the identified compounds present was confirmed using external standards adopting a simple, accurate, and rapid analytical HPLC method. The results showed that 100% and 50% MeOH extracts possessed bioactivity; one of which (the 50% MeOH extract) displayed potent activity in all in vitro bioassays. MeOH extract (50%) derived fraction C and hydroalcoholic fraction 5 (GAHAF5) were observed to possess higher antioxidant, antiinflammatory, and in vitro anticancer activity. IC50 of GAHAF5 against MCF-7, HEp-2, and NCI-H522 cancer cells was recorded as 26.2, 51.4, and 63 µg/mL, respectively. ESI-MS/MS and HPLC analysis identified catechin, chlorogenic acid, caffeic acid, and morin as potential bioactive compounds in the GAHAF5 fraction with concentrations of 1230, 491, 957, and 130 µg/g, respectively. The findings indicated that G. asiatica bioactive fractions possessed antiinflammatory activity in vitro and were cytotoxic against breast cancer, lung cancer, and laryngeal cancer cell lines.


Assuntos
Antioxidantes , Grewia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bioensaio , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem
11.
Antibiotics (Basel) ; 11(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35326875

RESUMO

The development of effective treatments against infectious diseases is an extensive and ongoing process due to the rapid adaptation of bacteria to antibiotic-based therapies. However, appropriately designed activity enhancers, including antibiotic delivery systems, can increase the effectiveness of current antibiotics, overcoming antimicrobial resistance and decreasing the chance of contributing to further bacterial resistance. The activity/delivery enhancers improve drug absorption, allow targeted antibiotic delivery, improve their tissue and biofilm penetration and reduce side effects. This review provides insights into various antibiotic activity enhancers, including polymer, lipid, and silver-based systems, designed to reduce the adverse effects of antibiotics and improve formulation stability and efficacy against multidrug-resistant bacteria.

12.
Foods ; 11(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35159528

RESUMO

Syzygium cumini, locally known as Jamun in Asia, is a fruit-bearing crop belonging to the Myrtaceae family. This study aims to summarize the most recent literature related to botany, traditional applications, phytochemical ingredients, pharmacological activities, nutrition, and potential food applications of S. cumini. Traditionally, S. cumini has been utilized to combat diabetes and dysentery, and it is given to females with a history of abortions. Anatomical parts of S. cumini exhibit therapeutic potentials including antioxidant, anti-inflammatory, analgesic, antipyretic, antimalarial, anticancer, and antidiabetic activities attributed to the presence of various primary and secondary metabolites such as carbohydrates, proteins, amino acids, alkaloids, flavonoids (i.e., quercetin, myricetin, kaempferol), phenolic acids (gallic acid, caffeic acid, ellagic acid) and anthocyanins (delphinidin-3,5-O-diglucoside, petunidin-3,5-O-diglucoside, malvidin-3,5-O-diglucoside). Different fruit parts of S. cumini have been employed to enhance the nutritional and overall quality of jams, jellies, wines, and fermented products. Today, S. cumini is also used in edible films. So, we believe that S. cumini's anatomical parts, extracts, and isolated compounds can be used in the food industry with applications in food packaging and as food additives. Future research should focus on the isolation and purification of compounds from S. cumini to treat various disorders. More importantly, clinical trials are required to develop low-cost medications with a low therapeutic index.

13.
J Ethnopharmacol ; 287: 114919, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-34995693

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels has been extensively used in the ancient medical system of Pakistan, India, Bangladesh, and Sri Lanka to combat diabetes, inflammation, and renal disorders. These health-promoting aspects of S. cumini are related to bioactive metabolites such as phenolic acids, anthocyanins, tannins, and flavonoids. AIM OF THE STUDY: Earlier to this study, we have reported S. cumini extracts as potential sources of bioactive compounds bearing antioxidant and anti-inflammatory properties. However, prior further suggesting S. cumini fruit extracts for consumption against inflammatory disorders, it was mandatory to validate the claim and explore toxicity of the extracts. This study aims to determine the in vivo anti-nociceptive, anti-inflammatory, acute, and subacute toxicity properties of S. cumini crude extracts, followed by identifying and quantifying bioactive metabolites. MATERIAL AND METHODS: In the present study, the anti-nociceptive and anti-inflammatory potential of S. cumini sequential crude extracts were evaluated using formalin and glutamate-induced paw licking method in mice. The acute and sub-acute toxicity assessment of active extract was performed by oral administration in rats. An acute toxicity trial was performed with two different doses, i.e., 2000 mg/kg and 3000 mg/kg for consecutive 14 days, whereas a sub-acute toxicity study was conducted at doses of 750 mg/kg and 1500 mg/kg for the next 28 days. Identification of bioactive compounds was performed using HPLC, and at the end, in silico docking calculations of identified compounds were performed. RESULTS: The 100% methanolic extract (SCME) protected the mice from painful stimulation of formalin and glutamate in a dose-dependent manner with the maximum effect of 49% and 67% at 200 mg/kg, respectively, followed by moderate and non-influential effects of 50% methanolic extract and dichloromethane (DCM) extracts when compared to control, i.e., normal saline. The results of acute toxicity recorded LD50 of SCME over 3000 mg/kg, and no antagonistic effects were recorded during the subacute study when SCME dispensed at the rate of 750 mg/kg and 1500 mg/kg. SCME was found to induce no adverse effects to kidney, heart, liver, spleen, and paired lungs examined by hematological, serum biochemical, histological analysis. HPLC analysis of S. cumini 100% methanolic extracts revealed the presence of delphinidin 3-glucoside, peonidin-3,5-diglucoside, scopoletin, and umbelliferone at the concentration of 127.4, 2104, 31.3, 10.4 µg/g whereas in 50% methanolic extract, the quinic acid, catechin, and myricetin were present at the concentration of 54.9, 63.7, 12.3 µg/g, respectively. Umbelliferone and scopoletin are newly reported compounds in the present study. In silico docking calculations of these compounds indicated the potential of anti-nociceptive and anti-inflammatory activities. CONCLUSIONS: These findings validate that S. cumini fruit extracts are a rich source of bioactive compounds that needs to be considered to enhance biological activities with lesser side effects.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Syzygium/química , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
14.
Nutrients ; 13(12)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34960117

RESUMO

Globally grown and organoleptically appreciated Grewia species are known as sources of bioactive compounds that avert the risk of communicable and non-communicable diseases. Therefore, in recent years, the genus Grewia has attracted increasing scientific attention. This is the first systematic review which focusses primarily on the nutritional composition, phytochemical profile, pharmacological properties, and disease preventative role of Grewia species. The literature published from 1975 to 2021 was searched to retrieve relevant articles from databases such as Google Scholar, Scopus, PubMed, and Web of Science. Two independent reviewers carried out the screening, selection of articles, and data extraction. Of 815 references, 56 met our inclusion criteria. G. asiatica and G. optiva were the most frequently studied species. We found 167 chemical compounds from 12 Grewia species, allocated to 21 categories. Flavonoids represented 41.31% of the reported bioactive compounds, followed by protein and amino acids (10.7%), fats and fatty acids (9.58%), ash and minerals (6.58%), and non-flavonoid polyphenols (5.96%). Crude extracts, enriched with bioactive compounds, and isolated compounds from the Grewia species show antioxidant, anticancer, anti-inflammatory, antidiabetic, hepatoprotective/radioprotective, immunomodulatory, and sedative hypnotic potential. Moreover, antimicrobial properties, improvement in learning and memory deficits, and effectiveness against neurodegenerative ailments are also described within the reviewed article. Nowadays, the side effects of some synthetic drugs and therapies, and bottlenecks in the drug development pathway have directed the attention of researchers and pharmaceutical industries towards the development of new products that are safe, cost-effective, and readily available. However, the application of the Grewia species in pharmaceutical industries is still limited.


Assuntos
Grewia/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Etnofarmacologia/métodos , Flavonoides/análise , Flavonoides/farmacologia , Frutas/química , Humanos , Hipnóticos e Sedativos/farmacologia , Hipoglicemiantes/farmacologia , Agentes de Imunomodulação/farmacologia , Camundongos , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Ratos , Sementes/química
15.
Biomolecules ; 11(10)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34680148

RESUMO

Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.


Assuntos
Dicetopiperazinas/química , Dipeptídeos/química , Neoplasias/tratamento farmacológico , Prolina/química , Dicetopiperazinas/uso terapêutico , Dipeptídeos/genética , Dipeptídeos/uso terapêutico , Descoberta de Drogas , Humanos , Neoplasias/genética , Peptídeos Cíclicos/química , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/uso terapêutico , Prolina/genética , Prolina/uso terapêutico
16.
Polymers (Basel) ; 13(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34372035

RESUMO

Much attention has been paid to chitosan biopolymer for advanced wound dressing owing to its exceptional biological characteristics comprising biodegradability, biocompatibility and respectable antibacterial activity. This study intended to develop a new antibacterial membrane based on quaternized aminochitosan (QAMCS) derivative. Herein, aminochitosan (AMCS) derivative was quaternized by N-(2-Chloroethyl) dimethylamine hydrochloride with different ratios. The pre-fabricated membranes were characterized by several analysis tools. The results indicate that maximum surface potential of +42.2 mV was attained by QAMCS3 membrane compared with +33.6 mV for native AMCS membrane. Moreover, membranes displayed higher surface roughness (1.27 ± 0.24 µm) and higher water uptake value (237 ± 8%) for QAMCS3 compared with 0.81 ± 0.08 µm and 165 ± 6% for neat AMCS membranes. Furthermore, the antibacterial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus cereus. Superior antibacterial activities with maximum inhibition values of 80-98% were accomplished by QAMCS3 membranes compared with 57-72% for AMCS membrane. Minimum inhibition concentration (MIC) results denote that the antibacterial activities were significantly boosted with increasing of polymeric sample concentration from 25 to 250 µg/mL. Additionally, all membranes unveiled better biocompatibility and respectable biodegradability, suggesting their possible application for advanced wound dressing.

17.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916198

RESUMO

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 µg/mL (against AChE) and 60 µg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 µg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 µg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.


Assuntos
Produtos Biológicos/química , Grewia/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Sítios de Ligação , Produtos Biológicos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ligação Proteica , Relação Estrutura-Atividade , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química
18.
J Ethnopharmacol ; 271: 113805, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33465442

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is an important medicinal plant utilized in the health care systems of Pakistan, India, Sri Lanka, and Bangladesh. S. cumini have been used to treat renal issues, indigestion, diabetes, dysentery, and employed in folk medicine to treat inflammations. It is known to anticipate antioxidant, anti-inflammatory, anticancer, anti-diabetic, anti-bacterial, antifungal, activities, and radioprotective activities. MATERIAL AND METHODS: We examined the in vitro anti-inflammatory activities of S. cumini fruit extracts, evaluated using membrane stabilization, egg albumin denaturation, and bovine serum albumin denaturation assays. In vivo anti-inflammatory activity was also assessed, using murine models of carrageenan, formaldehyde, and PGE2 induced paw edema. Fractionation of active extracts was performed using HPLC, followed by LC-ESI-MS/MS analysis to identify the bioactive compounds responsible for anti-inflammatory activity. RESULTS: The crude methanolic extract showed stronger in vitro and in vivo anti-inflammatory activities compared to other extracts. The most potent effects were observed in the formaldehyde induced paw edema assay wherein methanolic extract and standard indomethacin induced 72% and 88% inhibition against paw edema volume in comparison to control (normal saline) respectively. In the bovine serum albumin denaturation assay the methanolic extract induced 82% inhibition against denaturation as compared to control (phosphate buffer) while standard diclofenac sodium induced 98% inhibition. In contrast, 50% v/v MeOH:H2O or 100% dichloromethane extracts displayed moderate to weak effects in the anti-inflammatory models. HPLC fractionation provided 6 active sub-fractions, four (MF2, MF3, MF6, MF7) from the 100% methanolic extract and two (HAF1, HAF3) from the 50% methanolic extract. The MF2, MF7, and HAF1 sub-fractions displayed potent activity in all studied in vitro assays. LC-ESI-MS-MS analysis tentatively identified delphinidin 3-glucoside, peonidin-3,5-diglucoside, gallic acid, liquitrigenin, scopoletin, umbelliferon, and rosmanol from the 100% methanolic fractions. Myricetin, catechin, quinic acid, chlorogenic acid, ellagic acid, gallic acid, and caffeic acid were identified in the 50% methanolic fractions. CONCLUSIONS: These results demonstrate that S. cumini fruit extracts are a rich source of bioactive compounds that are worthy of further investigation as leads for anti-inflammatory drug discovery.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Syzygium/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Ásia , Modelos Animais de Doenças , Edema/induzido quimicamente , Traumatismos do Pé/induzido quimicamente , Traumatismos do Pé/tratamento farmacológico , Traumatismos do Pé/patologia , Frutas/química , Técnicas In Vitro , Medicina Tradicional , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Extratos Vegetais/uso terapêutico , Ratos Wistar
19.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467056

RESUMO

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.


Assuntos
Quitosana , Curcumina , Nanopartículas , Cápsulas , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico
20.
Methods Mol Biol ; 2103: 199-213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31879927

RESUMO

Octapeptins are naturally derived cyclic lipopeptide antibiotics with activity against a range of Gram-negative pathogens, including highly resistant strains. Octapeptin C4, an exemplar of the class, was synthesized using a combination of Fmoc solid-phase peptide synthesis (SPPS) and solution-phase cyclization. Utilizing H-L-Leu-2-chlorotrityl resin, peptide couplings were performed using HCTU and collidine in DMF. The linear sequence was terminated by N-acylation with 3-(R)-hydroxydecanoic acid. The residue Dab-2 was orthogonally protected with 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)isovaleryl group (ivDde) to enable selective side-chain deprotection prior to resin cleavage. Resin cleavage was accomplished with hexafluoroisopropanol in DCM, followed by cyclization with diphenylphosphoryl azide (DPPA) and solid sodium bicarbonate in DMF.


Assuntos
Lipopeptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Azidas , Técnicas de Química Sintética , Cromatografia Líquida de Alta Pressão , Ciclização , Hidrólise , Lipopeptídeos/isolamento & purificação , Estrutura Molecular , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia
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