Investigation of molecular design, synthesis, and biological assessment of new benzopyran derivatives

Mahesh Agasa Ramu; Somashekhar  Metri; Trupti A Hunnura; Koushallya Patil; Hanamant  B Sannakki

doi:10.69857/joapr.v13i1.722

Authors

Mahesh Agasa Ramu Department of Pharmaceutical Chemistry, The Oxford College of Pharmacy, Bengaluru, Karnataka, India https://orcid.org/0000-0003-4073-9021
Somashekhar Metri Department of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, India
Trupti A Hunnura Department of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, India
Koushallya Patil Department of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, India
Hanamant B Sannakki Department of Pharmaceutical Chemistry, BLDEA’S SSM College of Pharmacy and Research Centre, Vijayapura 586103, Karnataka, India

DOI:

https://doi.org/10.69857/joapr.v13i1.722

Keywords:

Anti-tubercular compounds, PKS13 (PDB ID: 5v3y), Molecular Docking, Benzopyran derivatives, Alamar blue susceptibility assay (MABA)

Abstract

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.

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