title: 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.affiliation: 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
authors.forename: Kavya
authors.initials: K
authors.lastname: Ramkumar
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Yarovenko
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Nikitina
authors.forename: Igor V
authors.initials: IV
authors.lastname: Zavarzin
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Krayushkin
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Kovalenko
authors.forename: Adrian
authors.initials: A
authors.lastname: Esqueda
authors.forename: Srinivas
authors.initials: S
authors.lastname: Odde
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: 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*
chemical_list: D019428:HIV Integrase Inhibitors; D012236:Rhodanine; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase