Design and Synthesis of Some Novel Fluorobenzimidazoles Substituted with Structural Motifs Present in Physiologically Active Natural Products for Antitubercular Activity

Document Type: Research article

Authors

1 Department of Pharmaceutical Chemistry, Vivekananda College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore-560055, Karnataka, India.

2 bDepartment of Pharmaceutical Chemistry, Nargund College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore-560085, Karnataka, India.

3 Department of Pharmaceutical Chemistry, Nargund College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore-560085, Karnataka, India.

4 Department of Molecular Biology and Immunology, Maratha Mandalʹs NGH Institute of Dental Sciences & Research Centre, Belgaum-590010, Karnataka, India.

Abstract

Keeping in view the drawbacks associated with research on anti-TB drugs based on plant extracts and the non-availability of fluorinated natural products with antitubercular activity has prompted us to make an effort towards the synthesis and characterization of a novel series of fifteen substituted fluorobenzimidazoles. The newly synthesized compounds were characterized by I.R, 1H-NMR, 13C-NMR, Mass and elemental analysis. The synthesized compounds 4(a-f) and 5(b-j) have been evaluated for their in-vitro antimycobacterial activity against H37Rv strain (ATCC 27294) by MABA method. Incorporation of methylenedioxyphenyl moiety at 2- and 6-position of the benzimidazole ring furnished compounds 4d and 5i with antitubercular activity comparable or more potent than the naturally occurring compounds with reported antitubercular activity. Among the fifteen tested compounds, 4d and 5i emerged as promising hits characterized by MIC lower than that determined for sesamin against the pathogenic H37Rv strain. Antitubercular activity results indicate that these compounds may be suitable for further lead optimization. The cytotoxic effect of these active compounds on THP-1 cell line was assessed by MTT assay and the results suggest that these two molecules are potential candidates for further development as antitubercular agents.

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