20.500.12556/RUL-167908 Navigating the chemical space of ENR Inhibitors a comprehensive analysis Antimicrobial resistance is a global health threat that requires innovative strategies against drug-resistant bacteria. Our study focuses on enoyl-acyl carrier protein reductases (ENRs), in particular FabI, FabK, FabV, and InhA, as potential antimicrobial agents. Despite their promising potential, the lack of clinical approvals for inhibitors such as triclosan and isoniazid underscores the challenges in achieving preclinical success. In our study, we curated and analyzed a dataset of 1412 small molecules recognized as ENR inhibitors, investigating different structural variants. Using advanced cheminformatic tools, we mapped the physicochemical landscape and identified specific structural features as key determinants of bioactivity. Furthermore, we investigated whether the compounds conform to Lipinski rules, PAINS, and Brenk filters, which are crucial for the advancement of compounds in development pipelines. Furthermore, we investigated structural diversity using four different representations: Chemotype diversity, molecular similarity, t-SNE visualization, molecular complexity, and cluster analysis. By using advanced bioinformatics tools such as matched molecular pairs (MMP) analysis, machine learning, and SHAP analysis, we were able to improve our understanding of the activity cliques and the precise effects of the functional groups. In summary, this chemoinformatic investigation has unraveled the FAB inhibitors and provided insights into rational antimicrobial design, seamlessly integrating computation into the discovery of new antimicrobial agents. antibacterial drug development enoyl-acyl carrier protein reductases ENR inhibitors antibiotic resistance Fab InhA bioinformatical analysis razvoj antibakterijskih zdravil enoil-acil nosilne proteinske reduktaze zaviralci ENR odpornost na antibiotike Fab InhA bioinformatska analiza rezistenca true false true Angleški jezik Slovenski jezik Članek v reviji 2025-03-20 08:47:46 2025-03-20 08:47:51 2025-03-21 03:57:49 0000-00-00 00:00:00 2024 0 0 27 str. iss. 3, art. 252 Vol. 13 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.015.8 2079-6382 10.3390/antibiotics13030252 229600771 antibiotics-13-00252.pdf antibiotics-13-00252.pdf 1 2959C80900D909B94448269AAD040991 7ff2f0fb3adc9201a54523d126b1b30c1909755d9e2ba51915b94a39dda665cb d95ad7b1-055e-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=200821 https://www.mdpi.com/2079-6382/13/3/252 1 9d5c8f4b-055e-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=200820 Fakulteta za farmacijo 0 0 0