title: Synthesis, biological evaluation and molecular modeling studies of new 2,3-diheteroaryl thiazolidin-4-ones as NNRTIs.
abstract: In a focused exploration, thiazolidin-4-ones with different C-2 and N-3 substituent groups were synthesized and evaluated as non-nucleoside reverse transcriptase inhibitors against HIV-1. This has led to new active compounds sporting heteroaryls at both C-2 and N-3 positions prompting to view them in the backdrop of nevirapine. To assign the molecular attributes for the activity, the compounds are investigated by docking them into non-nucleoside inhibitor-binding pocket of HIV-1 reverse transcriptase (RT). The most active compounds of this series (7d and 7f) shared spatial features with nevirapine with added molecular flexibility. Furthermore, in molecular dynamics simulations carried out for up to 10 ns, the compounds 7d and 7f showed consistency in their interactions with non-nucleoside inhibitor-binding pocket of HIV-1 RT and suggested Tyr319 and Val106 as potential residues for H-bond interaction with these molecules. These results open new avenues for the exploration of 2,3-diheteroaryl thiazolidin-4-ones for prevention of HIV-1.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.|Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, 226 026, India.
authors.forename: Utsab
authors.initials: U
authors.lastname: Debnath
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Verma
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Singh
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Rawat
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Toxicology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Tripathi
authors.affiliation: Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, 226 026, India.
authors.forename: Hefazat H
authors.initials: HH
authors.lastname: Siddiqui
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.
authors.forename: Seturam B
authors.initials: SB
authors.lastname: Katti
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226 031, India.
authors.forename: Yenamandra S
authors.initials: YS
authors.lastname: Prabhakar
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D053778:Thiazolidines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1 reverse transcriptase; molecular docking; molecular dynamics; non-nucleoside reverse transcriptase inhibitor; thiazolidin-4-one