Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors.
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.
Ramkumar
Kavya
K
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90033, USA. ramkumar@usc.edu
Yarovenko
Vladimir N
VN
Nikitina
Alexandra S
AS
Zavarzin
Igor V
IV
Krayushkin
Mikhail M
MM
Kovalenko
Leonid V
LV
Esqueda
Adrian
A
Odde
Srinivas
S
Neamati
Nouri
N
D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000037:antagonists & inhibitors; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D012236:Rhodanine / Q000138:chemical synthesis* / Q000737:chemistry*
D019428:HIV Integrase Inhibitors; D012236:Rhodanine; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase