Investigation of Antifungal Properties of Synthetic Dimethyl-4-Bromo-1-(Substituted Benzoyl) Pyrrolo[1,2-a] Quinoline-2,3-Dicarboxylates Analogues: Molecular Docking Studies and Conceptual DFT-Based Chemical Reactivity Descriptors and Pharmacokinetics Evaluation.

Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein ß-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation.

Effect of curcumin and quercetin on lysosomal enzyme activities in streptozotocin-induced diabetic rats.

BACKGROUND & AIMS: Diabetes causes impairment of various enzyme activities in the physiological system, including lysosomal enzymes. The effect of feeding curcumin, quercetin and aminoguanidine on lysosomal enzyme activities viz., N-acetyl-ß-d-glucosaminidase, ß-d-glucuronidase, ß-d-galactosidase and acid phosphatase were studied in different tissues of streptozotocin-induced diabetic rats. METHOD: Rats were divided into four control groups and four diabetic groups. Experimental groups were fed with diet supplemented with curcumin (0.5%) or quercetin (0.1%) or aminoguanidine (0.05%). Lysosomal enzyme activities were determined in various tissues. RESULTS: The specific activity of N-acetyl-ß-d-glucosaminidase in liver of diabetic rats was decreased when compared to control rats and was ameliorated with curcumin and quercetin treatment by 67% and 78%, respectively. On the other hand, ß-d-glucuronidase activity was higher in the brain of diabetic rats (0.90 ± 0.04 nmol/mg protein/min), when compared to control rats (0.45 ± 0.02 nmol/mg protein/min) and was decreased in curcumin (0.75 ± 0.05 nmol/mg protein/min) and quercetin (0.74 ± 0.11 nmol/mg protein/min) treated rats. ß-d-galactosidase activity in spleen of curcumin and quercetin fed diabetic group rats was ameliorated by 68% and 58%, respectively, in comparison to diabetic rats. Acid phosphatase activity in diabetic rats decreased in testis when compared to control. CONCLUSION: Curcumin and quercetin feeding modulated lysosomal enzyme activities in different tissues during diabetes and the effect was comparable to well-known anti-glycative agent - aminoguanidine.