Background: Effective inhibition of pathogenic bacterial urease activity aligned with satisfied dissolution of struvite stone by purified flavonoid moieties can overcome several lifethreatening renal disorders. Objective: The objective of this study was to investigate the in vitro inhibition of urease enzyme and an effective control over the formation of infectious renal stone (Struvite stone) by the extract and purified flavonoid of Citrus limon seeds. Methods: Standard spectrophotometry analysis to determine urease activity, Gel diffusion method for in vitro antibacterial activity, Artificial Neural Network (ANN) to validate the urease inhibitory activity, and LC-MS-PDA analysis to predict the structures of polyphenols were employed. Results: Complete urease inhibition was noticed in hot water extract (HWE) and 50% ethanolic extract, and an appreciable inhibition was recorded by preparative thin layer chromatography (PTLC) purified polyphenols (78.3±2.6%). A satisfactory struvite stone dissolution of about 49.6±3.2% and 40.9±2.1%, was recorded by HWE and PTLC eluate, respectively. ANN-based training model proved a significant correlation (r2 = 0.987) between the predicted and conducted experimental results of urease inhibitory activity. Two new novel polyphenols were identified (luteolin-7-0- rutinoside glycoside derivative [m/z 786] and an unknown compound [m/z 651]) through LC-MSPDA analysis. Likewise, simulated bioimplant coated with purified polyphenols recorded a satisfactory urease inhibitory activity. Conclusion: A correlated result of urease inhibition, growth inhibition against clinically significant bacterial pathogens, and in vitro struvite stone dissolution strongly support the efficacy of renoprotective effect of C. limon seeds.

Background: Breast cancer is the most prevalent cancer among women globally, characterized by the uncontrolled growth of breast cells, and remains a leading cause of cancer-related morbidity and mortality. It can occur in both men and women, though it is significantly rarer in men. The multifactorial nature of breast cancer involves genetic mutations, hormonal influences, and complex cellular signalling pathways. The disease is typically classified into different subtypes based on hormone receptor status, which influences treatment decisions. Early detection through regular screening, such as mammograms, and awareness of symptoms significantly improve prognosis. Treatment options vary based on the stage and type of breast cancer and may include surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy. Objective: We aimed to design novel compounds based on reported active pharmacophoric features and validate them through molecular modelling. These designed compounds were then synthesized and characterized. Finally, a biological evaluation of the synthesized compounds was performed to assess their efficacy. Method: Thirty compounds were designed based on a literature survey. Out of these compounds, twelve compounds were found good on the docking studies, and these twelve new derivatives (RD 01-12) were synthesized and subjected to in silico, in vitro (EGFR assay), and ADMET profiling to identify the most potent compound. Result: All 12 compounds were synthesised and characterised. Out of 12 compounds, RD-09 emerged as the most potent enzymatic assay with an IC50 value of 1.21 ± 0.03 µM, confirmed by docking studies; it possessed a docking score of -7.302 against the EGFR receptor. These compounds were further characterized using IR, 1H NMR, and mass spectrometry. Conclusion: Based on pharmacophoric features, twelve triazine-4-thiazolidinone derivatives (RD 01- 12) were designed, synthesized, and evaluated for their potential as EGFR-2 inhibitors, specifically targeting triple-negative breast cancer (TNBC). Among 12 synthesised compounds, compound RD- 09 demonstrated the most significant activity with an IC50 value of 1.21 ± 0.03 µM. Docking studies further supported its binding interaction with the catalytic domain of the EGFR receptor. The combined results from in vitro, in silico, and ADMET profiling suggest that RD-09 holds promise as a leading compound for further development in the treatment of TNBC.

Aim: The present study aimed to explore the hepatorenal efficacy of ethanolic and hydroalcoholic extract against Gentamicin and Cisplatin-induced toxicity in experimental rats. Background: The current research focuses on the characterization and evaluation of the hepatorenal efficacy of P.granatum extracts on cellular and tissue models, particularly in terms of its restorative actions following cytotoxic damage induced by Gentamicin and Cisplatin. This work builds upon several key areas of contemporary scientific research. Objective: The objective of the current investigation was to establish an association of oxidative stress in hepatorenal insufficiency caused by Gentamicin and Cisplatin xenobiotics and its amelioration with the antioxidant activity of ethanolic extract of Punica granatum (EEPG) and hydroalcoholic extract of Punica granatum (HAEPG). Methods: Using ascorbic acid as a standard, the in vitro antioxidant activity of EEPG and HAEPG was assessed using the DPPH method. The hepatorenal efficiency of the EEPG and HAEPG were studied in Gentamicin and Cisplatin-induced models. The hepatorenal toxicity was induced by 100mg/kg/day i.p. of Gentamicin for 12 days and 1.5mg/kg/day i.p. cisplatin for 3 weeks in Wistar albino rats. Lipid profile, serum hepatorenal markers, and hepatorenal tissue oxidative markers such as, CAT, MDA, GSH, and SOD were estimated to assess the extent of hepatorenal efficiency. Using Masson trichrome (MT) stained tissue sections, renal and hepatic tissue damage was assessed. The degree of renal tissue damage was evaluated using tubular necrosis, perivascular edema, intratubular proteinaceous cast, and vascular congestion. Result: In vitro studies have shown that the HAEPG containing higher total phenolic and flavonoid content, exhibits greater antioxidant activity compared to the EEPG. The severity of hepatotoxicity and renal toxicity was found to be more severe in cisplatin than Gentamicin. The Cisplatin treatment more severely affects the level of CAT, GSH, and SOD, respectively compared to Gentamicin induction. Cisplatin also significantly decreased SOD and increased MDA levels. Treatment with EEPG and HAEPG demonstrated beneficial effects by reducing the levels of oxidative enzymes, which contributes to the restoration of hepatorenal damage due to their antioxidant properties.The MT panels of the treated groups revealed and supported hepatorenal regenerative changes. Conclusion: The antioxidant properties of EEPG and HAEPG showed beneficial effects and ameliorated the levels of tissue hepatorenal oxidative enzymes and were found to possess restoration of hepatorenal damage in a dose-dependent manner.

Aim: A 2D QSAR study of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) inhibitors revealed that electronic, topological, and steric properties are important structural features required for activity against ACAT. Background: In order to interpret the evidence encrypted by the molecular structure of the compounds, a standard physicochemical descriptors-centered, and Quantitative Structure-Activity Relationship (QSAR) approach was implemented on a data set of Indoline derivatives were reported to be acyl-coenzyme A (CoA): cholesterol acyltransferase ACAT inhibitors. Objective: The ACAT enzyme plays an important role in the absorption of dietary cholesterol. Therefore, the inhibition of ACAT is a key strategy or primary objective for the treatment of hypercholesterolemia and atherosclerosis. Method: Chemo metric models were designed by inserting a battery of statistical techniques in the current study that demonstrate the linear approaches of analysis, including multiple linear regression (MLR), partial least square PLS, and non-linear methods such as artificial neural networks (ANN). Result: The activity contributions of these molecules were analyzed through regression equation, and the best QSAR model was created with an excellent correlative and predictive ability. Significant statistical values S = 0.35, F = 60.30, r = 0.92, r² = 0.85, r² (CV) = 0.82 of the designed models were obtained using stepwise MLR and a comparable PLS and FFNN model with r² (CV) = 0.82, 0.88 and 0.86 respectively and the relevant descriptors like inertia moment 1 size, Kier Chiv4 (cluster) index, Kier Chiv6(ring) index offered important information regarding this model. Conclusion: The model reveals that inertia moment 1 size, Kier Chiv4 (cluster) index, and Kier Chiv6 (ring) index are prerequisite descriptors to determine other promising ACAT antagonists with high and liable potency against the target. Therefore, these characteristics may be used efficiently for the design and evaluation of active compounds as new ACAT inhibitors thanks to their utilization.

Background: Diabetes prevalence is progressively rising everywhere, particularly in developing countries. Lichens have evolved into a rich source of innovative bioactive chemicals with their anti-oxidant capabilities, widening the scope of well-documented and effective diabetes treatment. Objective: The main objectives of this study were to perform in vitro alpha-amylase, alphaglucosidase inhibition analysis, and anti-oxidant of lichen Physica aipolia. Method: Folin Ciocalteu’s reagent was used to determine the total phenolic content for biological activities. The Aluminum trichloride method was used to determine total flavonoid content, and the free radical assay method was used to determine the antioxidant activity of P. aipolia using 2,2- diphenyl-1-picrylhydrazyl (DPPH). Moreover, substrate 2-Chloro-4-nitrophenyl-α-D-maltotrioside (CNPG3) and substrate-nitrophenyl-α-D-glucopyranose (p-NPG) were used for the determination of alpha-amylase and alpha-glucosidase inhibition activities respectively, and molecular docking was performed by Auto Dock Vina. Results: Total phenolic and flavonoid contents present in P. aipolia were 37.41 ± 2.87 mg GAE/g and 5.53 ± 0.95 mg QE/g, respectively. For anti-oxidant inhibition activity, crude extract of methanol showed an IC50 value of 15.324 ± 0.80 μg/mL. Furthermore, a methanolic crude extract showed significant inhibition activities against alpha-amylase (IC50 = 178.50 ± 1.10 μg/mL) and alphaglucosidase (IC50 = 76.10 ± 0.91 μg/mL). During in silico analysis, zeorin showed an effective binding affinity with -7.9 kcal/mol, and Atranorin showed -7.4 kcal/mol in the orthosteric site of the protein. Conclusion: Physica aipolia exhibits the potential to impact biological functions, demonstrating antidiabetic properties, as confirmed by molecular docking analysis in silico.

: In this modern era, the environment is being contaminated with toxic pollutants as a result of anthropogenic activities. To overcome the harmful effects of pollutants, scientists have developed ideas and technologies. Biotechnology provides a green approach for decontaminating the environment, i.e., bioremediation. Several organisms have been explored for their enzymes. Enzymes belonging to various classes are useful for degrading, transforming, or removal of pollutants. Oxidoreductases produced by different plants, bacteria, and fungi are useful for deterioration of toxic pollutants, like compounds having aroma, called aromatic compounds (benzene, chlorine, phenols, phenanthrene, etc.), PAHs (Polyaromatic Hydrocarbons), various dyes, etc. Oxidoreductases are further classified as laccases, peroxidases, and oxygenases. All three classes have proven to be efficacious in the field of bioremediation. Microorganism strains have also been genetically engineered for the production of enzymes. Oxidoreductases can be used to remove pollutants from industrial waste. This review has classified all the species that produce oxidoreductase enzymes, their mechanism of action, and the pollutants that have been removed by using oxidoreductases.

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: The aim is to systematize data from literature sources on the study of changes in the activity of HMGR enzymes and lipid metabolism under the influence of cyclic lactones, identify among them new potential inhibitors of HMGR and formulate hypotheses about the details of the mechanism of action of the enzyme in relation to the product - mevalonolactone.