2-(Aryl)-3-furan-2-ylmethyl-thiazolidin-4-ones as selective HIV-RT Inhibitors

• Published in: Bioorganic & medicinal chemistry 2005-12, Vol.13 (24), p.6771-6776
• Main Authors: Rawal, Ravindra K., Prabhakar, Yenamandra S., Katti, S.B., De Clercq, E.
• Format: Article
• Language: English
• Subjects: 4-thiazolidinones; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cell Line; Dicyclohexylcarbodiimide; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - metabolism; HIV-1 - drug effects; HIV-1 - enzymology; HIV-1 - physiology; HIV-RT; Humans; Medical sciences; Molecular Structure; NNRTIs; Pharmacology. Drug treatments; QSAR; Quantitative Structure-Activity Relationship; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.07.063

In the present study, 4-thiazolidinones have been assembled by DCC-mediated three-component reaction of amine, aldehyde and mercapto acetic acid and tested as HIV-RT inhibitors. A series of 4-thiazolidinones were evaluated as selective inhibitors of the HIV-RT enzyme. Our attempt in correlating the derived physicochemical properties with the HIV-RT inhibitory activity resulted in some statistically significant QSAR models with good predictive ability. The QSAR studies indicated the role of lipophilicity, dipole moment and out-of-plane potential energy of the compounds in rationalizing the activity. One of the compounds, 1, inhibited the enzyme at 0.204 μM concentration with minimal toxicity to MT-4 cells.