Non Nucleoside Reverse Transcriptase Inhibitors, Molecular Docking Studies and Antitubercular Activity of Thiazolidin-4-one Derivatives

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Author(s): Trupti S. Chitre*, Shital M. Patil, Anagha G. Sujalegaonkar, Kalyani D. Asgaonkar, Vijay M. Khedkar, Dinesh R. Garud, Prakash C. Jha, Sharddha Y. Gaikwad, Smita S. Kulkarni, Amit Choudhari, Dhiman Sarkar.

Journal Name: Current Computer-Aided Drug Design

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Background: Management of Co-existence of Acquired immunodeficiency syndrome and Tuberculosis has become a global challenge due to emergence of resistant strains and pill burden.

Objective: Hence aim of the present work was to design and evaluate compounds for their dual activity on HIV-1 and tuberculosis (TB).

Method: A series of seven, novel Thiazolidin-4-one derivatives were synthesized and evaluated for their anti-HIV and anti-tubercular activity alogwith Molecular docking studies. All the seven compounds displayed promising activity against the replication of HIV-1 in cell-based assays. The four most active compounds were further evaluated against X4 tropic HIV-1UG070 and R5 tropic HIV-1VB59 primary isolates. Binding affinity of all the designed compounds for HIV-RT and Mycobacterium tuberculosis Enol Reductase (MTB InhA) was gauged by molecular docking studies which revealed crucial thermodynamic interactions governing their binding.

Result: The CC50 values for the test compounds were in the range of, 15.08-34.9 µg/ml while the IC50 values were in the range of 16.1-27.13(UG070; X4) and 12.03-23.64 (VB59; R5) µg/ml. The control drug Nevirapine (NVP) exhibited CC50 value of 77.13 µg/ml and IC50 value of 0.03 µg/ml. Amongst all these compounds, compound number 3 showed significant activity with a TI value of 2.167 and 2.678 against the HIV-1 X4 and the R5 tropic virus respectively. In anti-mycobacterial screening compounds proved effective in inhibiting the growth of both log phase and starved MTB cultures.

Conclusion: Compound 3 has been found to be active against HIV-1 as well as MTB.

Keywords: Non nucleoside Reverse Transcriptase, Human Immunodeficiency Virus-1, Anti-HIV-1 activity, Antitubercular activity, Molecular Docking, Thiazolidin-4-ones.

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(E-pub Ahead of Print)
DOI: 10.2174/1573409915666181221102903
Price: $95

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