Novel Furan Coupled Quinoline Diamide Hybrid Scaffolds as Potent Antitubercular Agents: Design, Synthesis and Molecular Modelling.
| Title: | Novel Furan Coupled Quinoline Diamide Hybrid Scaffolds as Potent Antitubercular Agents: Design, Synthesis and Molecular Modelling. |
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| Authors: | Rajpurohit A; Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur-577548, Chikkamagalur District, Karnataka, India.; Satyanarayan ND; Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur-577548, Chikkamagalur District, Karnataka, India.; Pathak L; Department of Pharmaceutical Chemistry, Al-Ameen College of Pharmacy, Bengaluru- 560027, Karnataka, India.; Ayyanar S; Department of Inorganic Chemistry, School of Chemistry, Madurai Kamaraj University, Palkalai Nagar, Madurai-625 021, Tamil Nadu St, India.; Rishinaradamangalam CR; Department of Inorganic Chemistry, School of Chemistry, Madurai Kamaraj University, Palkalai Nagar, Madurai-625 021, Tamil Nadu St, India.; Shoorapani P; Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur-577548, Chikkamagalur District, Karnataka, India. |
| Source: | Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2020; Vol. 16 (4), pp. 507-516. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101240303 Publication Model: Print Cited Medium: Internet ISSN: 1875-6638 (Electronic) Linking ISSN: 15734064 NLM ISO Abbreviation: Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Bentham Science Publishers; Original Publication: Sharjah, U.A.E.; San Francisco, CA : Bentham Science Publishers |
| MeSH Terms: | Drug Design* ; Molecular Docking Simulation*; Antitubercular Agents/*chemistry ; Antitubercular Agents/*pharmacology ; Furans/*chemistry ; Quinolines/*chemistry ; Quinolines/*pharmacology; Amides/chemistry ; Antitubercular Agents/chemical synthesis ; Antitubercular Agents/metabolism ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/enzymology ; Quinolines/chemical synthesis ; Quinolines/metabolism ; Transferases/chemistry ; Transferases/metabolism ; Microbial Sensitivity Tests ; Protein Conformation |
| Abstract: | Background: A novel series of 2-[(2-{[2-(furan-2-yl) quinolin-4-yl] carbonyl} hydrazinyl) carbonyl] benzoic acid, -4-oxobut-2-enoic acid and -4-oxobutanoic acids were synthesized and screened for in vitro antitubercular activity.; Objectives: In the present investigation, we describe the synthesis and biological screening of furan C-2 quinoline coupled diamides for antitubercular activity.; Methods: The mycobacterium tuberculai testing was carried out by MABA method and molecular docking studies were done by open-source molecular docking program, Autovina, using Pyrx 0.8 interface.; Results: The results revealed that the compounds inhibited the growth of H37Rv strain at concentrations as low as 1.6 to 12 µg/ml. Molecular binding of furan, quinoline and diamide (FQD) derivatives on five targets was good and these compounds fit very well within the binding domain of the target protein.; Conclusion: The synthesized FQD derivatives exhibited moderate to good inhibition activity especially compounds 5f, 5b and 8a exhibited very good inhibition activity due to the presence of three different scaffolds, such as INH, phenyl ketobutyric acid and fluoroquinolines. Hybridized molecules might have multiple modes of action / inhibit more than one tubercular target and could pave way for novel drug discovery in the field of tuberculosis.; (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| Contributed Indexing: | Keywords: Antitubercular and MABA method; carbonyl benzoic acid; fluoroquinolines; furan; phenyl ketobutyric acid; quinoline- 4-carboxylic acid. |
| Substance Nomenclature: | 0 (Amides); 0 (Antitubercular Agents); 0 (Furans); 0 (Quinolines); EC 2.- (Transferases) |
| Entry Date(s): | Date Created: 20190905 Date Completed: 20210118 Latest Revision: 20210118 |
| Update Code: | 20260130 |
| DOI: | 10.2174/1573406415666190904124630 |
| PMID: | 31483232 |
| Database: | MEDLINE |
Journal Article