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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Kavya RamkumarNouri Neamati

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.

References

Feb 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·F D Bushman, R Craigie
Jan 1, 1996·Journal of Pharmaceutical Sciences·K PalmP Artursson
Mar 14, 1997·Journal of Medicinal Chemistry·M C NicklausY Pommier
Jan 23, 1998·Journal of Medicinal Chemistry·M KawakamiL B Chen
Oct 29, 2000·Journal of Medicinal Chemistry·W J EganJ J Baldwin
Mar 29, 2001·Journal of Pharmacological and Toxicological Methods·C A Lipinski
May 11, 2001·The Journal of Biological Chemistry·R Craigie
Mar 30, 2002·Advanced Drug Delivery Reviews·William J Egan, Georgio Lauri
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Jan 7, 2005·Journal of Medicinal Chemistry·Raveendra DayamNouri Neamati
Jun 18, 2005·Bioorganic & Medicinal Chemistry Letters·Neil S CutshallMarina Prezhdo
Dec 13, 2005·Journal of Medicinal Chemistry·Raveendra DayamNouri Neamati
Nov 7, 2006·Bioorganic & Medicinal Chemistry·Fedora GrandeNouri Neamati
Feb 3, 2007·Current Pharmaceutical Design·Jinxia DengNouri Neamati
Feb 27, 2007·Expert Reviews in Molecular Medicine·Nick Vandegraaff, Alan Engelman
May 16, 2007·Reviews in Medical Virology·Vasu Nair, Guochen Chi
Jun 15, 2007·Molecular Aspects of Medicine·Melissa L Fishel, Mark R Kelley
Jul 14, 2007·Mini Reviews in Medicinal Chemistry·Guisen ZhaoHongxiang Lou
Nov 6, 2007·Medicinal Research Reviews·Raveendra DayamNouri Neamati
Jan 29, 2008·Chemical Biology & Drug Design·Sherida L JohnsonMaurizio Pellecchia
Feb 20, 2008·Journal of Medicinal Chemistry·Raveendra DayamNouri Neamati
Feb 29, 2008·Bioorganic & Medicinal Chemistry Letters·Mark W IrvineSimon J MacKenzie
Dec 17, 2008·Journal of Medicinal Chemistry·Zahrah ZawahirNouri Neamati
Feb 24, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Charles Hicks, Roy M Gulick
May 16, 2009·Current Medicinal Chemistry·T Tomasić, L P Masic
Aug 10, 2010·Core Evidence·Kavya Ramkumar, Nouri Neamati

❮ Previous
Next ❯

Citations

Sep 27, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nguyen Tien CongPing-Chung Kuo
Dec 3, 2014·European Journal of Medicinal Chemistry·Surender Singh JadavVenkatesan Jayaprakash
May 2, 2012·Bioorganic & Medicinal Chemistry·Abhishek Kumar JainRam Kishore Agrawal

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis

Software Mentioned

Schrödinger LigPrep
ADMET Predictor
Schrödinger
GOLD ( Genetic Optimization for Ligand Docking ; )
Glide
Image Quant
GOLD
Catalyst
Glide ( Grid - Based Ligand Docking With Energetics )
ChemScore

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.