دورية أكاديمية
أعرض في EDS

Design, synthesis, computational molecular docking studies of novel heterocyclics bearing 1,2,4-triazole, 1,3,4-oxadiazole conjugates as potent antibacterial and antitubercular agents.

التفاصيل البيبلوغرافية
العنوان: Design, synthesis, computational molecular docking studies of novel heterocyclics bearing 1,2,4-triazole, 1,3,4-oxadiazole conjugates as potent antibacterial and antitubercular agents.
المؤلفون: Sravanthi B; Department of Chemistry, GITAM School of Sciences, GITAM University, Visakhapatnam, India.; Department of Chemistry, Institute of Aeronautical Engineering, Hyderabad, India., Himavathi G; Department of Chemistry, GITAM School of Sciences, GITAM University, Visakhapatnam, India., Robert AR; Department of Chemistry, GITAM School of Sciences, GITAM University, Visakhapatnam, India., Karunakar P; Department of Biotechnology, Dayananda Sagar College of Engineering (Affiliated to Visvesvarava Technological University), Bangalore, India., Kiran KS; Department of Physics, Faculty of Engineering and Technology, Jain University, Bangalore, India., Maddila S; Department of Chemistry, GITAM School of Sciences, GITAM University, Visakhapatnam, India.; School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Durban, South Africa.
المصدر: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Jul; Vol. 42 (10), pp. 5376-5389. Date of Electronic Publication: 2023 Jun 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE
أسماء مطبوعة: Publication: June 2012- : Oxon, UK : Taylor & Francis
Original Publication: Guilderland, NY : Adenine Press, [c1983-
مواضيع طبية MeSH: Molecular Docking Simulation* , Triazoles*/chemistry , Triazoles*/pharmacology , Oxadiazoles*/chemistry , Oxadiazoles*/pharmacology , Antitubercular Agents*/pharmacology , Antitubercular Agents*/chemistry , Antitubercular Agents*/chemical synthesis , Microbial Sensitivity Tests* , Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/chemistry , Anti-Bacterial Agents*/chemical synthesis , Drug Design*, Molecular Dynamics Simulation ; Structure-Activity Relationship ; Heterocyclic Compounds/chemistry ; Heterocyclic Compounds/pharmacology ; Hydrogen Bonding ; Bacteria/drug effects
مستخلص: Herein, we report the synthesis, and characterization of a new series of 1,3,4-oxadiazole and 1,2,4-triazole derivatives based on azaindole acetamides and assigned as potential antibacterial and antitubercular substances. The structures of these compounds were established by 1 H NMR, 13 C NMR, and HRMS spectral analysis. In preliminary antibacterial studies, analogues 6b , 6d , and 6e were found to be most effective against S. aureus with MIC of 12.5, 6.25, and 12.5 μg/mL, whereas 8d displayed excellent activity against S. aureus, B. subtilis, E. coli bacterial strains with zones of inhibition 12.5, 25, and 12.5 μg/mL respectively. Particularly, the prepared scaffolds 8c , 8d , and 8e showed remarkable antifungal activity with MIC value 12.5, 12.5, and 6.25 μg/mL against A. flavus and 6d , 6c producing an increase in the activity against C. Albicans with zones of inhibition 12.5 and 12.5 μg/mL respectively. Also, through the antitubercular studies, we found that compounds 6e and 8b have a strong activity with M. tuberculosis H 37 Rv with MICs 3.26, and 6.48 μg/mL, respectively. The protein stability, fluctuations of APO-Protein, and protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3, and potential lead molecules were identified. Our findings were further confirmed using molecular docking, revealing that azaindole based ligand 6e, 6f, and 8a has strong hydrophobic Tyr179, Trp183, Ile177, Ile445, and H-bondings interactions Arg151 and Arg454 through molecular dynamics simulation studies, making it potential biological compound. These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME.Communicated by Ramaswamy H. Sarma.
فهرسة مساهمة: Keywords: 1,2,4–triazoles; 1,3,4–oxadiazoles; ADMET; antibacterial activity; antifungal activity; docking analysis; tuberculosis
المشرفين على المادة: 0 (1,2,4-triazole)
0 (1,3,4-oxadiazole)
تواريخ الأحداث: Date Created: 20230621 Date Completed: 20240519 Latest Revision: 20240519
رمز التحديث: 20240520
DOI: 10.1080/07391102.2023.2226743
PMID: 37340639
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-0254
DOI:10.1080/07391102.2023.2226743