Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors

Molecules

Kavya Ramkumar¹  Vladimir N. Yarovenko¹  Alexandra S. Nikitina¹  Igor V. Zavarzin¹  Mikhail M. Krayushkin¹  Leonid V. Kovalenko¹  Adrian Esqueda¹  Srinivas Odde¹ 

[1] ¹Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90033, USA

关键词: rhodanine;    HIV-1;    integrase;    APE1;    2-thioxo-4-thiazolidinone;    docking;   

DOI  :  10.3390/molecules15063958

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.