Bioorganic and Medicinal Chemistry Reports

Since COVID-19 epidemic began, no effective medication have been found to treat this disease. In the current study, several peroxisome proliferator-activated receptor (PPAR) agonist drugs, including fenofibrate, binifibrate, bezafibrate, ciprofibrate, clofibrate, gemfibrozil, pioglitazone, and rosiglitazone  were selected, and the molecular docking studies were applied by using main protease (Mpro), human angiotensin-converting enzyme 2 (ACE2), and transmembrane protease serine 2 (TMPRSS2) targets. The chemical structures of selected drugs were retrieved from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). AutoDock 4.2 molecular docking program was used to obtain best binding interactions of selected drugs. Visualization of the docking results was performed using BIOVIA Discovery Studio Visualizer and PyMol. As a result, rosiglitazone and binifibrate  were found to be an effective drugs against SARS-CoV-2 main protease (Mpro) with binding energies of –6.8 and -6.7 kcal/mol, respectively. Bezafibrate and binifibrate  were found to be an effective drugs against ACE2 with binding energies of -8.6 kcal/mol, respectively.  On the other hand, fenofibrate, bezafibrate and rosiglitazone showed highest binding energies against TMPRSS2 protein as compared  with reference drugs favipiravir, chloroquine, and hydroxychloroquine. Our in silico results suggest that PPAR agonist drugs warrant further investigation as potential lead molecules for discovering more potent compounds in anti-CoV drug development research.

2-Styrylchromones are very potent bioactive substances showing innumerable activities like antioxidant, antidiabetic, antiviral, antiinflammatory, anticancer, anti-microbial etc. All these activities are due to their core structure (benz-γ-pyrone) containing styryl group at 2nd position. Substituents especially hydroxyl groups are responsible for anti-diabetic and antioxidant activities. 2-Styrylchromones with a greater number of –OH substituents showed high activity than the remaining compounds. Compounds 5, 6, 7 and 9 having significant activity where the nature and position of substituents play a vital role. The synthetic compound with –OH groups at 4', 6 and 7 positions competed with standard drugs in respective activities.

The rising resistance to antimicrobial drugs has highlighted the urgent need for discovering novel compounds with diverse mechanisms of action that can target both sensitive and resistant strains. To address this, we developed some chalcone analogs. In this study, a series of compounds (12-15) featuring fluoro and trifluoromethyl groups on the B ring were synthesized and evaluated for their antimicrobial properties. The positions of the substituents on the B ring were altered to assess their impact on antimicrobial activity. Compounds 13 and 14 demonstrated potent antibacterial activity (MIC = 15.6 and 7.81 μg/mL, respectively) against Staphylococcus aureus. Overall, our findings highlight Compounds 13 and 14 as promising scaffolds warranting further optimization for the development of effective antibacterial agents.

 For screening purposes, there has been interest in creating natural product scaffolds that closely resemble drug-like compounds utilizing combinatorial chemical approaches. Various screening techniques are being developed to improve the data mining and drug development campaigns' usage of natural materials. From the tissue extract of the freshwater crab Barytelphusa cunicularis, four chemicals were shown to have biological activity against both gram-positive and gram-negative bacteria, including E. coli and B. subtilis, and S. aureus. Four pathogens were used in this study: A. niger, M. furfur, A. flavus, and P. Chrysosporium. Flavus and P. Chrysosporium, but poorly against A. Niger and M. Furfur. To further the development of potential therapeutics, structure-activity relationship (SAR) analysis via a virtual screening protocol was conducted. Bioactivity assessments confirmed the compounds' efficacy against both bacterial and fungal targets. Molecular docking analyses revealed that all four organic compounds exhibit favorable absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties and bind with the protein DNA gyrase at diverse sites. In conclusion, the compounds' notable activity with DNA gyrase suggests their potential for drug design exploration.