Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives
Background: Tuberculosis (TB) remains a global health challenge, necessitating the discovery of novel anti-tubercular agents. The N-(8-hydrazinyl-3,4-dihydro-2H-1-benzopyran-6-yl)-N'-phenyl urea (HSM-II) scaffold has shown potential in developing effective drug candidates. Objective: This study...
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Creative Pharma Assent
2025-02-01
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| Series: | Journal of Applied Pharmaceutical Research |
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| Online Access: | https://japtronline.com/index.php/joapr/article/view/722 |
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| author | Mahesh Agasa Ramu Somashekhar Metri Trupti A Hunnura Koushallya Patil Hanamant B Sannakki |
| author_facet | Mahesh Agasa Ramu Somashekhar Metri Trupti A Hunnura Koushallya Patil Hanamant B Sannakki |
| author_sort | Mahesh Agasa Ramu |
| collection | DOAJ |
| description | Background: Tuberculosis (TB) remains a global health challenge, necessitating the discovery of novel anti-tubercular agents. The N-(8-hydrazinyl-3,4-dihydro-2H-1-benzopyran-6-yl)-N'-phenyl urea (HSM-II) scaffold has shown potential in developing effective drug candidates. Objective: This study aimed to design and evaluate 50 derivatives of HSM-II for their anti-tubercular activity, focusing on compounds demonstrating strong interactions with the protein PKS13 (PDB ID: 5v3y). Methods: A series of derivatives was synthesized, starting with the reaction of 8-bromo-3,4-dihydro-2H-1-benzopyran-6-amine and phenyl carbamic acid, yielding six new benzopyran derivatives. These were further treated with various aromatic halides to produce the HSM-II derivatives. Molecular docking studies were performed to identify compounds with high binding affinity to PKS13. Promising candidates (HSM-II-3, HSM-II-13, HSM-II-27, HSM-II-33, HSM-II-42, and HSM-II-49) were selected for biological evaluation. Anti-tubercular activity was assessed in vitro using the Alamar Blue Susceptibility Test (MABA) against Mycobacterium tuberculosis H37Rv and H37Ra strains. Results: Docking studies revealed high binding scores for the selected compounds, indicating strong interactions with the target protein. In vitro evaluations demonstrated significant anti-tubercular activity for the majority of synthesized derivatives. The pharmacologic profile of the compounds suggests potential as lead candidates for further optimization. Conclusion: This study presents the design, synthesis, and biological evaluation of 50 diverse derivatives of N-(8-hydrazinyl-3,4-dihydro-2H-1-benzopyran-6-yl)-N'-phenyl urea (HSM-II). Six derivatives (HSM-II-3, HSM-II-13, HSM-II-27, HSM-II-33, HSM-II-42, and HSM-II-49) demonstrated high binding affinities with PKS13 (PDB ID: 5v3y), with scores reaching -11.4 kcal/mol, and potent in vitro anti-tubercular activity, as assessed using the Alamar Blue Susceptibility Assay (MABA). Prominent derivatives exhibited MIC values significantly lower than those of standard drugs like rifampicin. |
| format | Article |
| id | doaj-art-caec5588d4a8436c97625f4de3c4c6a0 |
| institution | OA Journals |
| issn | 2348-0335 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Creative Pharma Assent |
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| series | Journal of Applied Pharmaceutical Research |
| spelling | doaj-art-caec5588d4a8436c97625f4de3c4c6a02025-08-20T02:00:43ZengCreative Pharma AssentJournal of Applied Pharmaceutical Research2348-03352025-02-01131869410.69857/joapr.v13i1.722723Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivativesMahesh Agasa Ramu0https://orcid.org/0000-0003-4073-9021Somashekhar Metri1Trupti A Hunnura2Koushallya Patil3Hanamant B Sannakki4Department of Pharmaceutical Chemistry, The Oxford College of Pharmacy, Bengaluru, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, IndiaBackground: Tuberculosis (TB) remains a global health challenge, necessitating the discovery of novel anti-tubercular agents. The N-(8-hydrazinyl-3,4-dihydro-2H-1-benzopyran-6-yl)-N'-phenyl urea (HSM-II) scaffold has shown potential in developing effective drug candidates. Objective: This study aimed to design and evaluate 50 derivatives of HSM-II for their anti-tubercular activity, focusing on compounds demonstrating strong interactions with the protein PKS13 (PDB ID: 5v3y). Methods: A series of derivatives was synthesized, starting with the reaction of 8-bromo-3,4-dihydro-2H-1-benzopyran-6-amine and phenyl carbamic acid, yielding six new benzopyran derivatives. These were further treated with various aromatic halides to produce the HSM-II derivatives. Molecular docking studies were performed to identify compounds with high binding affinity to PKS13. Promising candidates (HSM-II-3, HSM-II-13, HSM-II-27, HSM-II-33, HSM-II-42, and HSM-II-49) were selected for biological evaluation. Anti-tubercular activity was assessed in vitro using the Alamar Blue Susceptibility Test (MABA) against Mycobacterium tuberculosis H37Rv and H37Ra strains. Results: Docking studies revealed high binding scores for the selected compounds, indicating strong interactions with the target protein. In vitro evaluations demonstrated significant anti-tubercular activity for the majority of synthesized derivatives. The pharmacologic profile of the compounds suggests potential as lead candidates for further optimization. Conclusion: This study presents the design, synthesis, and biological evaluation of 50 diverse derivatives of N-(8-hydrazinyl-3,4-dihydro-2H-1-benzopyran-6-yl)-N'-phenyl urea (HSM-II). Six derivatives (HSM-II-3, HSM-II-13, HSM-II-27, HSM-II-33, HSM-II-42, and HSM-II-49) demonstrated high binding affinities with PKS13 (PDB ID: 5v3y), with scores reaching -11.4 kcal/mol, and potent in vitro anti-tubercular activity, as assessed using the Alamar Blue Susceptibility Assay (MABA). Prominent derivatives exhibited MIC values significantly lower than those of standard drugs like rifampicin.https://japtronline.com/index.php/joapr/article/view/722anti-tubercular compoundspks13 (pdb id: 5v3y)molecular dockingbenzopyran derivativesalamar blue susceptibility assay (maba) |
| spellingShingle | Mahesh Agasa Ramu Somashekhar Metri Trupti A Hunnura Koushallya Patil Hanamant B Sannakki Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives Journal of Applied Pharmaceutical Research anti-tubercular compounds pks13 (pdb id: 5v3y) molecular docking benzopyran derivatives alamar blue susceptibility assay (maba) |
| title | Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives |
| title_full | Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives |
| title_fullStr | Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives |
| title_full_unstemmed | Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives |
| title_short | Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives |
| title_sort | investigation of molecular design synthesis and biological assessment of new benzopyran derivatives |
| topic | anti-tubercular compounds pks13 (pdb id: 5v3y) molecular docking benzopyran derivatives alamar blue susceptibility assay (maba) |
| url | https://japtronline.com/index.php/joapr/article/view/722 |
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