Lead optimization at C-2 and N-3 positions of thiazolidin-4-ones as HIV-1 non-nucleoside reverse transcriptase inhibitors

Vanangamudi Murugesan, Vinay S. Tiwari, Reshu Saxena, Rajkamal Tripathi, Ramesh Paranjape, Smita Kulkarni, Nandini Makwana, Rahul Suryawanshi, Seturam B. Katti

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Based on rational drug design approach, a series of novel thiazolidin-4-ones bearing different aryl/heteroaryl moieties at position C-2 and N-3 are synthesized and evaluated as potent inhibitors for human immunodeficiency virus type-1 reverse transcriptase enzyme (HIV-1 RT). An in vitro HIV-1 RT assay showed that the compounds 4, 5, 6, 8, 12, 13, 14 and 17 have shown high inhibition of reverse transcriptase (75.41, 95.50, 98.07, 91.24, 85.27, 77.59, 84.11 & 76.49% inhibition) enzyme activity. Further, cell based assay showed that compounds 4, 5, 8 & 12 are identified as the best compounds of the series (EC 50 ranged from 0.09 to 0.8 μg/ml and 0.12 to 1.06 μg/ml) against HIV-1 III B and HIV-1 ADA5 strains, respectively. Moreover, the compounds which were active against HIV-1 III B and HIV-1 ADA5 were also found to be active against primary isolates (EC 50 ranged from 0.10 to 1.55 μg/ml against HIV-1 UG070 and 0.07 to 1.1 μg/ml against HIV-1 VB59), respectively. Structure-activity relationship (SAR) studies demonstrated the importance of the lipophilic bulky substituent pattern on compact heteroaryl ring at N-3, replacement of C4′ at C-2 phenyl by trivalent bioisosteric nitrogen and dihalo groups at C-2 aryl/heteroaryl of thiazolidin-4-ones is crucial for anti-HIV-1 activity. Molecular modeling of compounds 4, 5, 8 and 12 in complex with HIV-1 RT demonstrate that there is good correlation of results obtained from SAR studies. Therefore the compounds 4, 5, 8 and 12 may be considered as good candidates for further optimization of anti-HIV-1 activity.

Original languageEnglish
Pages (from-to)6919-6926
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number22
StatePublished - 15 Nov 2011
Externally publishedYes


  • Anti-HIV-1 activity
  • HIV-1 reverse transcriptase
  • NNRTIs
  • Thiazolidin-4-ones

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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