Evaluation of 4-thiazolidinone derivatives as potential reverse transcriptase inhibitors against HIV-1 drug resistant strains

Bioorg Chem. 2017 Apr;71:211-218. doi: 10.1016/j.bioorg.2017.02.007. Epub 2017 Feb 15.


Rapid emergence of drug resistance is crucial in management of HIV infection limiting implementation of efficacious drugs in the ART regimen. Designing new molecules against HIV drug resistant strains is utmost essential. Based on the anti-HIV-1 activity, we selected four 4-thiazolidinone derivatives (S009-1908, S009-1909, S009-1911, S009-1912) and studied their interaction with reverse transcriptase (RT) from a panel of 10 clinical isolates (8 nevirapine resistant and two susceptible) using in silico methods, and inhibition pattern using in vitro cell based assays. On the basis of binding affinity observed in in silico analysis, 2-(2-chloro-6-nitrophenyl)-3-(4, 6-dimethylpyridin-2-yl) thiazolidin-4-one (S009-1912) was identified as the lead molecule followed by S009-1908, S009-1909 and S009-1911. The in vitro activity against the same panel was assessed using TZM-bl assay (IC50: 0.4-11.44µg/ml, TI: 4-126) and subsequently in PBMC assay against a nevirapine resistant clinical isolate (IC50: 0.8-6.65µg/ml, TI: 8.31-11.43) and standard strain from NIH ARRRP (IC50: 0.95-3.6µg/ml, TI: 9-26). The study shows analogue with pyrimidin-2-yl amino substitution at N-3 position of thiazolidin-4-one ring (S009-1908, S009-1909, S009-1911) exhibited enhanced activity as compared to pyridin-2-yl substituted derivatives (S009-1912), suggesting the use 4-thiazolidinones for developing potent inhibitors against HIV-1 drug resistant strains.

Keywords: 4-thiazolidinone; Drug resistant; HIV-1; Reverse transcriptase.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line
  • Drug Resistance, Viral
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Leukocytes, Mononuclear / virology
  • Molecular Docking Simulation
  • Reverse Transcriptase Inhibitors / chemistry*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiazolidines / chemistry*
  • Thiazolidines / pharmacology*


  • 4-thiazolidinone
  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Thiazolidines
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase