Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors.

Abstract

Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties.

• Authors: Kavya Ramkumar, Vladimir N Yarovenko, Alexandra S Nikitina, Igor V Zavarzin, Mikhail M Krayushkin, Leonid V Kovalenko, Adrian Esqueda, Srinivas Odde, Nouri Neamati
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 15 Issue 6 Pg. 3958-92 (Jun 01 2010) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 20657419 (Publication Type: Journal Article)

Chemical References

• HIV Integrase Inhibitors
• Rhodanine
• APEX1 protein, human
• DNA-(Apurinic or Apyrimidinic Site) Lyase

Topics

• DNA-(Apurinic or Apyrimidinic Site) Lyase (antagonists & inhibitors)
• HIV Integrase Inhibitors (chemical synthesis, chemistry)
• Humans
• Molecular Structure
• Rhodanine (chemical synthesis, chemistry)