Author/Authors :
Dixit, Sheshagiri R. Novel Drug Design and Discovery Laboratory - Department of Pharmaceutical Chemistry - Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, India , Joshi, Shrinivas D. Novel Drug Design and Discovery Laboratory - Department of Pharmaceutical Chemistry - Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, India , Kulkarni, Venkatarao H. Novel Drug Design and Discovery Laboratory - Department of Pharmaceutical Chemistry - Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, India , Jalalpure, Sunil S. Basic Science Research Centre - KLE University, Belagavi - 590010, Karnataka, India , Kumbar, Vijay M. Basic Science Research Centre - KLE University, Belagavi - 590010, Karnataka, India , Mudaraddi, Tulasigiriyappa Y. Basic Science Research Centre - KLE University, Belagavi - 590010, Karnataka, India , Nadagouda, Mallikarjuna N. Novel Drug Design and Discovery Laboratory - Department of Pharmaceutical Chemistry - Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, India , minabhavi, Tejraj M. A Novel Drug Design and Discovery Laboratory - Department of Pharmaceutical Chemistry - Soniya Education Trust’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad-580 002, India
Abstract :
Introduction:
In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.
Method & Materials:
Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from Mycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway of M. tuberculosis and also it is an important target for designing novel anti-TB agents.
Results:
Among the synthesized compounds, compounds 4g and 4i showed H-bonding interactions with MET98, TYR158 and co-factor NAD+, all of which fitted well within the binding pocket of InhA. Also, these compounds have shown the same type of interaction as that of 4TZK ligand. The compounds were further evaluated for preliminary anti-TB activities against M. tuberculosis H37Rv strain.
Conclusion:
Some compounds were also screened for their mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic.
Keywords :
Surflex docking , Cytotoxicity , Antitubercular activity , Pyrazoline carbaldehyde
