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Liver inflammatory diseases are marked by serious complications. Notably, nicardipine (NCD) has demonstrated anti-inflammatory properties, but its benefits in liver inflammation have not been studied yet. However, the therapeutic efficacy of NCD is limited by its short half-life and low bioavailability. Therefore, we aimed to evaluate the potential of NCD-loaded chitosan nanoparticles (ChNPs) to improve its pharmacokinetic profile and hepatic accumulation. Four formulations of NCD-ChNPs were synthesized and characterized. The optimal formulation (NP2) exhibited a mean particle diameter of 172.6 ± 1.94 nm, a surface charge of +25.66 ± 0.93 mV, and an encapsulation efficiency of 88.86 ± 1.17 %. NP2 showed good physical stability as a lyophilized powder over three months. It displayed pH-sensitive release characteristics, releasing 77.15 ± 5.09 % of NCD at pH 6 (mimicking the inflammatory microenvironment) and 52.15 ± 3.65 % at pH 7.4, indicating targeted release in inflamed liver tissues. Pharmacokinetic and biodistribution studies revealed that NCD-ChNPs significantly prolonged NCD circulation time and enhanced its concentration in liver tissues compared to plain NCD. Additionally, the study investigated the protective effects of NCD-ChNPs in thioacetamide-induced liver injury in rats by modulating the NFκB/NLRP3/IL-1ß signaling axis. NCD-ChNPs effectively inhibited NFκB activation, reduced NLRP3 inflammasome activation, and subsequent release of IL-1ß, which correlated with improved hepatic function and reduced inflammation and oxidative stress. These findings highlight the potential of NCD-ChNPs as a promising nanomedicine strategy for the treatment of liver inflammatory diseases, warranting further investigation into their clinical applications, particularly in hypertensive patients with liver inflammatory conditions.
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Therapeutics that interfere with the damage/pathogen-associated molecular patterns (DAMPs/PAMPs) have evolved as promising candidates for hepatic inflammation like that occurring in non-alcoholic fatty liver disease (NAFLD). In the current study, we examined the therapeutic impact of the phosphodiesterase-1 inhibitor vinpocetine (Vinpo), alone or when combined with Lactobacillus, on hepatic abnormalities caused by a 13-week high-fat diet (HFD) and diabetes in rats. The results show that Vinpo (10 and 20 mg/kg/day) dose-dependently curbed HFD-induced elevation of liver injury parameters in serum (ALT, AST) and tissue histopathology. These effects were concordant with Vinpo's potential to ameliorate HFD-induced fibrosis (Histological fibrosis score, hydroxyproline, TGF-ß1) and oxidative stress (MDA, NOx) alongside restoring the antioxidant-related parameters (GSH, SOD, Nrf-2, HO-1) in the liver. Mechanistically, Vinpo attenuated the hepatocellular release of DAMPs like high mobility group box (HMGB)1 alongside lowering the overactivation of the pattern recognition receptors including, toll-like receptor (TLR)4 and receptor for advanced glycation end-products (RAGE). Consequently, there was less activation of the transcription factor nuclear factor-kappa B that lowered production of the proinflammatory cytokines TNF-α and IL-6 in Vinpo-treated HFD/diabetes rats. Compared to Vinpo treatment alone, Lactobacillus probiotics as adjunctive therapy with Vinpo significantly improved the disease-associated inflammation and oxidative stress injury, as well as the insulin resistance and lipid profile abnormalities via enhancing the restoration of the symbiotic microbiota. In conclusion, combining Vinpo and Lactobacillus probiotics may be a successful approach for limiting NAFLD in humans.
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Doxorubicin (DOX) is an anthracycline chemotherapy drug widely employed in the treatment of various cancers, known for its potent antineoplastic properties but often associated with dose-dependent cardiotoxicity, limiting its clinical use. This review explores the complex molecular details that determine the heart-protective effectiveness of carvedilol in relation to cardiotoxicity caused by DOX. The harmful effects of DOX on heart cells could include oxidative stress, DNA damage, iron imbalance, disruption of autophagy, calcium imbalance, apoptosis, dysregulation of topoisomerase 2-beta, arrhythmogenicity, and inflammatory responses. This review carefully reveals how carvedilol serves as a strong protective mechanism, strategically reducing each aspect of cardiac damage caused by DOX. Carvedilol's antioxidant capabilities involve neutralizing free radicals and adjusting crucial antioxidant enzymes. It skillfully manages iron balance, controls autophagy, and restores the calcium balance essential for cellular stability. Moreover, the anti-apoptotic effects of carvedilol are outlined through the adjustment of Bcl-2 family proteins and activation of the Akt signaling pathway. The medication also controls topoisomerase 2-beta and reduces the renin-angiotensin-aldosterone system, together offering a thorough defense against cardiotoxicity induced by DOX. These findings not only provide detailed understanding into the molecular mechanisms that coordinate heart protection by carvedilol but also offer considerable potential for the creation of targeted treatment strategies intended to relieve cardiotoxicity caused by chemotherapy.
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Cardiotoxicidad , Carvedilol , Doxorrubicina , Carvedilol/farmacología , Carvedilol/uso terapéutico , Humanos , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Doxorrubicina/efectos adversos , Doxorrubicina/toxicidad , Animales , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/toxicidad , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Carbazoles/farmacología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Propanolaminas/farmacologíaRESUMEN
In this study, biochar (BC) from Delonix regia pods peel and gum from Delonix regia seed (SG) were prepared, and also biochar/chitosan composite (BCS) and biochar/Delonix regia seed gum/chitosan composite (BCGS) were fabricated for the efficient adsorption of phenol. Various characterization tools such as SEM, TEM, ATR-FTIR, TGA, zeta potential, and textural investigation were studied to examine the features of the synthetized adsorbents, confirming their positive construction. It was fully studied how necessary factors, comprising pH, dose of adsorbent, contact shaking time, initial phenol concentration, and temperature influenced adsorption behavior. An obvious rise of the adsorption capacity from 60.16 to 165.20 mg/g was achieved by the modification of biochar with Delonix regia seed gum and chitosan under ideal circumstances of 2 h contact duration, pH 7, 15 °C, and a dose of 2.0 g/L. The phenol adsorption was well applied by Langmuir, Temkin, Dubinin-Radushkevich, and Sips isotherms, in addition to nonlinear pseudo-second-order kinetic model. Furthermore, the physisorption, endothermic, and spontaneous process was illustrated by thermodynamic investigation. Additionally, the fabricated adsorbents could be effectively used and regenerated without main losses of only 7.5, 4.6, and 4.0 % for BC, BCS, and BCGS, respectively in the removal percentage after seven cycles of application.
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Carbón Orgánico , Quitosano , Fenol , Gomas de Plantas , Semillas , Quitosano/química , Carbón Orgánico/química , Adsorción , Semillas/química , Concentración de Iones de Hidrógeno , Cinética , Fenol/química , Gomas de Plantas/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Temperatura , Purificación del Agua/métodos , Agua/química , TermodinámicaRESUMEN
Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.
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Carcinoma Hepatocelular , Proteínas Hedgehog , Itraconazol , Neoplasias Hepáticas , Transducción de Señal , Sorafenib , Sorafenib/farmacología , Sorafenib/uso terapéutico , Proteínas Hedgehog/metabolismo , Humanos , Animales , Transducción de Señal/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Ratones , Itraconazol/farmacología , Itraconazol/uso terapéutico , Apoptosis/efectos de los fármacos , Masculino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Sinergismo Farmacológico , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Resistencia a Antineoplásicos/efectos de los fármacos , Autofagia/efectos de los fármacosRESUMEN
Malathion (MAL) is one of the highly toxic organophosphorus (OP) compounds that induces hepatotoxicity. Echinops. ritro leaves extract (ERLE) is traditionally used in the treatment of bacterial/fungal infections. This study's goal was to investigate the potential of extracts from ERLE against hepatotoxicity induced by MAL in male albino rats. Four equal groups of forty mature male albino rats were created: The rats in the first group used as a control. The second group of rats received ERLE orally. The third group received MAL. ERLE and MAL were administered to the fourth group of rats. Six-week treatment groups were conducted. Using lipid peroxidation indicators [malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], apoptotic markers [Bcl-2 & caspase-3] and tumor necrosis factor alpha (TNF-α). Rats treated with MAL underwent a significant increase on MDA, ALT, AST, caspase-3 and TNF-α marker with a significant decrease in antioxidant markers [CAT, SOD, GPx] and Bcl-2. Histologically, MAL-treated group's liver sections displayed damaged hepatocytes with collapsed portions, pyknotic nuclei, vacuolated cytoplasm, and congested central veins. Ultra structurally, rat livers treated with MAL showed dilated cisternae of endoplasmic reticulum, swollen mitochondria with disrupted cristae, nuclei with disrupted chromatin content, multiple lysosomes, multiple vacuolations and a disrupted blood sinusoid. With rats treated with ERLE, these alterations were essentially non-existent. It is possible to conclude that ERLE protects against MAL hepatotoxicity, and that this protection is related, at least in part, to its antioxidant activities.
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Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas , Malatión , Estrés Oxidativo , Extractos Vegetales , Animales , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Masculino , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Ratas , Malatión/toxicidad , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Antioxidantes/farmacología , Alanina Transaminasa/sangre , Peroxidación de Lípido/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Asteraceae/químicaRESUMEN
An extensive range of new biologically active morpholine based thiosemicarbazones derivatives 3a-r were synthesized, characterized by spectral techniques and evaluated as inhibitors of ENPP isozymes. Most of the novel thiosemicarbazones exhibit potent inhibition towards NPP1 and NPP3 isozymes. Compound 3â¯h was potent inhibitor of NPP1 with IC50 value of 0.55⯱â¯0.02. However, the most powerful inhibitor of NPP3 was 3e with an IC50 value of 0.24⯱â¯0.02. Furthermore, Lineweaver-Burk plot for compound 3â¯h against NPP1 and for compound 3e against NPP3 was devised through enzymes kinetics studies. Molecular docking and in silico studies was also done for analysis of interaction pattern of all newly synthesized compounds. The results were further validated by molecular dynamic (MD) simulation where the stability of conformational transformation of the best protein-ligand complex (3e) were justified on the basis of RMSD and RMSF analysis.
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Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Morfolinas , Hidrolasas Diéster Fosfóricas , Pirofosfatasas , Tiosemicarbazonas , Morfolinas/química , Morfolinas/farmacología , Morfolinas/síntesis química , Hidrolasas Diéster Fosfóricas/química , Hidrolasas Diéster Fosfóricas/metabolismo , Pirofosfatasas/antagonistas & inhibidores , Pirofosfatasas/química , Pirofosfatasas/metabolismo , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Tiosemicarbazonas/síntesis química , Humanos , Cinética , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Fosfodiesterasa/síntesis química , Simulación por Computador , Relación Estructura-Actividad , LigandosRESUMEN
Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.
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One of the main goals of medicinal chemistry in recent years has been the development of new enzyme inhibitors and anti-cancer medicines. The isokaempferide' ability to inhibit the enzymes urease, elastase, and collagenase were also studied. The results showed that isokaempferide was the most effective compound against the assigned enzymes, with IC 50 values of 23.05 µM for elastase, 12.83 µM for urease, and 33.62 µM for collagenase respectively. It should be emphasized that natural compound was more effective at inhibiting some enzymes. Additionally, the compound was tested for their anti-cancer properties using colon, lung, breast cancer cell lines. The chemical activities of isokaempferide against urease, collagenase, and elastase were investigated utilizing the molecular docking study. The anti-cancer activities of the compound were evaluated against lung cancer cells such as SPC-A-1, SK-LU-1, 95D, breast cancer cells like MCF7, Hs 578Bst, Hs 319.T, and UACC-3133 cell lines, and colon cancer cell lines like CL40, SW1417, LS1034, and SW480. The chemical activities of isokaempferide against some of the expressed surface receptor proteins (EGFR, estrogen receptor, CD47, progesterone receptor, folate receptor, CD44, HER2, CD155, CXCR4, CD97, and endothelin receptor) in the mentioned cell lines were assessed using the molecular docking calculations. The results showed the probable interactions and their characteristics at an atomic level. The docking scores revealed that isokaempferide has a strong binding affinity to the enzymes and proteins. In addition, the compound formed powerful contact with the enzymes and receptors. Thus, isokaempferide could be potential inhibitor for enzymes and cancer cells.
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Neoplasias de la Mama , Flavonoides , Ureasa , Humanos , Femenino , Ureasa/metabolismo , Simulación del Acoplamiento Molecular , Células MCF-7 , Elastasa Pancreática/metabolismo , Colagenasas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.
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Nanopartículas del Metal , Extractos Vegetales , Humanos , Extractos Vegetales/química , Tecnología Química Verde , Plantas , Medicina Tradicional , Nanopartículas del Metal/química , Atención a la SaludRESUMEN
In the current study, three novel 1,4-phenylenediamine-based chromophores (3a-3c) were synthesized and characterized and then their nonlinear optical (NLO) characteristics were explored theoretically. The characterization was done by spectroscopic analysis, i.e. FT-IR, UV-Visible, and NMR spectroscopy, and elemental analysis. Notably, these chromophores exhibited UV-Visible absorption within the range of 378.635-384.757 nm in acetonitrile solvent. Additionally, the FMO findings for 3a-3c revealed the narrowest band gap (4.129 eV) for 3c. The GRPs for these chromophores were derived from HOMO-LUMO energy values, which showed correspondence with FMO results by depicting a minimum hardness (2.065 eV) for 3c. Among these compounds, 3c displayed the highest nonlinear behavior with maximum µtot, ßtot and γtot values of 4.79 D, 8.00 × 10-30 and 8.13 × 10-34 a.u., respectively. Our findings disclosed that the synthesized 1,4-phenylenediamine chromophores may be considered promising candidates for nonlinear optical materials, showing potential applications in the realm of optoelectronic devices.
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A lot of research has been done on using natural items as diabetes treatment. The molecular docking study was conducted to evaluate the inhibitory activities of urolithin A against α-amylase, α-glucosidase, and aldose reductase. The molecular docking calculations indicated the probable interactions and the characteristics of these contacts at an atomic level. The results of the docking calculations showed the docking score of urolithin A against α-amylase was -5.169 kcal/mol. This value for α-glucosidase and aldose reductase was -3.657 kcal/mol and -7.635 kcal/mol, respectively. In general, the outcomes of the docking calculations revealed that urolithin A can construct several hydrogen bonds and hydrophobic contacts with the assessed enzymes and reduces their activities considerably. The properties of urolithin against common human breast cancer cell lines, i.e., SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE were evaluated. The IC50 of the urolithin was 400, 443, 392, 418, 397, 530, 566 and 551 against SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE, respectively. After doing the clinical trial studies, the recent molecule may be used as an anti-breast cancer supplement in humans. IC50 values of urolithin A on α-amylase, α-glucosidase, and aldose reductase enzymes were obtained at 16.14, 1.06 and 98.73 µM, respectively.
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Aldehído Reductasa , Neoplasias de la Mama , Humanos , Femenino , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/química , alfa-Amilasas/química , alfa-Amilasas/metabolismo , Neoplasias de la Mama/tratamiento farmacológicoRESUMEN
Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU-C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14-19 and 5-119 µM for α-amylase and α-glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α-amylase: 14.37 µM and IC50 for α-glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α-amylase and α-glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic-level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.
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Antocianinas , Neoplasias , Fenilpropionatos , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/química , alfa-Amilasas , AntibacterianosRESUMEN
Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme.
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Diabetes Mellitus , Inhibidores de Glicósido Hidrolasas , Humanos , Estructura Molecular , Relación Estructura-Actividad , Hidrazonas/farmacología , Hidrazonas/química , alfa-Glucosidasas/metabolismo , Simulación del Acoplamiento Molecular , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
We synthesized novel pyrido[2,3-b]pyrazin based heterocyclic compounds (4-7) and their chemical structures were ascertained by spectral techniques (NMR, FT-IR). Besides experimental investigation, density functional theory (DFT) computations with B3LYP/6-31G(d,p) level of theory were executed to obtain spectroscopic and electronic properties. Nonlinear optical (NLO) properties, frontier molecular orbitals (FMOs), UV-visible, vibrational analysis, natural bond orbitals (NBOs), transition density matrix (TDM) and density of states (DOS) analyses of molecules (4-7) were accomplished at B3LYP/6-31G (d,p) level. Global reactivity parameters (GRPs) were correlated with the band gap (Egap) values; compound 7 with lower Egap (3.444 eV), exhibited smaller value of hardness (1.722 eV) with greater softness value (0.290 eV-1). The dipole moment (µ), average polarizability ãαã, first (ßtot) and second ãγã hyper-polarizabilities were calculated for compounds (4-7). Compound 7 showed less Egap, highest absorption wavelength and remarkable NLO response. The highest ãαã, ßtot and ãγã values for compound 7 were observed as 3.90 × 10-23, 15.6 × 10-30 and 6.63 × 10-35 esu, respectively. High NLO response revealed that pyrido[2,3-b]pyrazin based heterocyclic compounds had very remarkable contributions towards NLO technological applications. Further compounds (4-7) are utilized for the first time in electrochemical sensing of DNA, in vitro antioxidant and antiurease activity.
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Microbial compost plays a crucial role in improving soil health, soil fertility, and plant biomass. These biofertilizers, based on microorganisms, offer numerous benefits such as enhanced nutrient acquisition (N, P, and K), production of hydrogen cyanide (HCN), and control of pathogens through induced systematic resistance. Additionally, they promote the production of phytohormones, siderophore, vitamins, protective enzymes, and antibiotics, further contributing to soil sustainability and optimal agricultural productivity. The escalating generation of organic waste from farm operations poses significant threats to the environment and soil fertility. Simultaneously, the excessive utilization of chemical fertilizers to achieve high crop yields results in detrimental impacts on soil structure and fertility. To address these challenges, a sustainable agriculture system that ensures enhanced soil fertility and minimal ecological impact is imperative. Microbial composts, developed by incorporating characterized plant-growth-promoting bacteria or fungal strains into compost derived from agricultural waste, offer a promising solution. These biofertilizers, with selected microbial strains capable of thriving in compost, offer an eco-friendly, cost-effective, and sustainable alternative for agricultural practices. In this review article, we explore the potential of microbial composts as a viable strategy for improving plant growth and environmental safety. By harnessing the benefits of microorganisms in compost, we can pave the way for sustainable agriculture and foster a healthier relationship between soil, plants, and the environment.
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Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a-3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.
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Diabetes Mellitus , Tiosemicarbazonas , Humanos , Inhibidores de Glicósido Hidrolasas/química , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/metabolismo , Cinética , Tiosemicarbazonas/farmacología , Hipoglucemiantes/química , Diabetes Mellitus/tratamiento farmacológico , Cumarinas/química , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues' redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity.
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Introduction: One of the plants that has long been considered by humans is Equisetum arvense L. Equisetum arvense L is now recommended for external use to heal wounds and for internal use to relieve urinary tract and prostate disorders. In the current study, the antioxidant, cytotoxicity, and anti-human lung cancer properties of Equisetum arvense were investigated in in vitro conditions. Material and methods: Total phenolic content, total flavonoid content, radical scavenging activity, and ferrous ion chelating were assessed to evaluate the antioxidant activity. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was chosen to investigate anticancer activity of the plant extract. Results: The plant extract scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a free radical with an IC50 of 12.3 ±0.7 µg/ml better than positive controls. The plant was also rich in phenolic compounds with an amount of 396.2 ±3.2 mg GAE/g for total phenolic content. In the MTT assay, human colorectal carcinoma (HCT-8 [HRT-18], Ramos.2G6.4C10, HT-29, and HCT 116) and normal cell lines (HUVEC) were used to study the cytotoxicity and anticancer potential of Equisetum arvense L against human colorectal cancer. Conclusions: The cell viability of Equisetum arvense L was very low against human colorectal carcinoma cell lines without any cytotoxicity towards the normal (HUVEC) cell line. The best anti-human colorectal carcinoma properties of Equisetum arvense L against the above cell lines were observed in the case of the HT 29 cell line.