Next Article in Journal
A New Azaphilone, Kasanosin C, from an Endophytic Talaromyces sp. T1BF
Next Article in Special Issue
Lead Generation and Optimization Based on Protein-Ligand Complementarity
Previous Article in Journal
Synthesis, Characterization and Biological Studies of Some Novel Thieno[2,3-d]pyrimidines
Previous Article in Special Issue
4D-QSAR: Perspectives in Drug Design
Molecules 2010, 15(6), 3958-3992; doi:10.3390/molecules15063958
Article

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

1
, 2
, 3, 2, 2, 3, 1
, 1
 and 1,*
1 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90033, USA 2 N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky avenue, 47, 119991 Moscow, Russia 3 D.I. Mendeleev Russian University for Chemical Technology, Miusskaya sq., 9, 125047 Moscow, Russia
* Author to whom correspondence should be addressed.
Received: 8 March 2010 / Revised: 13 May 2010 / Accepted: 15 May 2010 / Published: 1 June 2010
(This article belongs to the Special Issue Structure-Based Drug Design)
Download PDF [3759 KB, uploaded 18 June 2014]

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.
Keywords: rhodanine; HIV-1; integrase; APE1; 2-thioxo-4-thiazolidinone; docking rhodanine; HIV-1; integrase; APE1; 2-thioxo-4-thiazolidinone; docking
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Ramkumar, K.; Yarovenko, V.N.; Nikitina, A.S.; Zavarzin, I.V.; Krayushkin, M.M.; Kovalenko, L.V.; Esqueda, A.; Odde, S.; Neamati, N. Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors. Molecules 2010, 15, 3958-3992.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert