Benzenesulfonohydrazide-tethered non-fused and fused heterocycles as potential anti-mycobacterial agents targeting enoyl acyl carrier protein reductase (InhA) with antibiofilm activity.
| Autor: | Al-Warhi T; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia., Sabt A; Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre Dokki Cairo 12622 Egypt., Korycka-Machala M; Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences Lodz Poland jdziadek@cbm.pan.pl., Kassem AF; Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University Al-Kharj 11942 Saudi Arabia., Shaldam MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University Kafrelsheikh 33516 Egypt wagdy2000@gmail.com., Ibrahim HAA; Pediatric Department, Faculty of Medicine, Cairo University Cairo Egypt., Kawka M; Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland., Dziadek B; Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland., Kuzioła M; Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences Lodz Poland jdziadek@cbm.pan.pl.; Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences Lodz Poland., Eldehna WM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University Kafrelsheikh 33516 Egypt wagdy2000@gmail.com.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria Canal El Mahmoudia St. Alexandria 21648 Egypt., Dziadek J; Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences Lodz Poland jdziadek@cbm.pan.pl. |
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| Jazyk: | angličtina |
| Zdroj: | RSC advances [RSC Adv] 2024 Sep 23; Vol. 14 (41), pp. 30165-30179. Date of Electronic Publication: 2024 Sep 23 (Print Publication: 2024). |
| DOI: | 10.1039/d4ra05616g |
| Abstrakt: | Because resistant variants of the disease are always emerging, tuberculosis is a global issue that affects economies. New antitubercular medications should be developed, and this can be done by inhibiting druggable targets. Enoyl acyl carrier protein (ACP) reductase (InhA) is a crucial enzyme for the survival of Mycobacterium tuberculosis (MTB). In this study, a series of small molecules based on non-fused and fused heterocycles (pyridine, coumarin, quinoline, and indole) tethered with benzenesulfonohydrazide were prepared via an aza-Michael reaction exploiting a one-pot synthesis approach. The synthesized molecules (2-7) were evaluated for their activity against tubercle bacilli. Three analogues showed efficacy against tuberculosis, with compound 7 demonstrating a MIC value as low as 8 μg mL -1 . Consequently, compounds 3 and 7 successfully hindered the growth of mycobacteria in human monocyte-derived macrophages (MDMs), demonstrating their ability to penetrate human professional phagocytes. Furthermore, they restricted the ability of mycobacteria to produce biofilms. In addition, the inhibitory effects of compounds 3 and 7 against InhA were assessed. Compound 7 exhibited the best efficacy, with an IC Competing Interests: No potential conflicts of interest was reported by the author(s). (This journal is © The Royal Society of Chemistry.) |
| Databáze: | MEDLINE |
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