Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines

Journal of Medicinal Chemistry
Katerina OtrubovaShelli R McAlpine

Abstract

We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating multiple drug-resistant colon cancers.

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Oct 19, 2006·Journal of the American Chemical Society·Markus HellerHorst Kessler
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Citations

Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicholas R WaterfieldRichard H Ffrench-Constant
Aug 19, 2014·Bioscience, Biotechnology, and Biochemistry·Hee-Seok LeeChan Lee
Feb 8, 2018·Oxidative Medicine and Cellular Longevity·Jignesh LunagariyaShihai Xu
Oct 8, 2009·Angewandte Chemie·Javier Ruiz-RodríguezFernando Albericio
Sep 8, 2010·Organic & Biomolecular Chemistry·José Antonio Morales-SernaJorge Cárdenas
Dec 11, 2013·Organic & Biomolecular Chemistry·Hendra WahyudiShelli R McAlpine
Nov 20, 2012·Angewandte Chemie·Jayanta ChatterjeeHorst Kessler
Mar 14, 2017·International Journal of Molecular Sciences·Defa BaiShihai Xu
Jan 26, 2016·ChemMedChem·Yen Chin KoayShelli R McAlpine
Jul 15, 2018·Journal of Pharmaceutical and Biomedical Analysis·Jie-Tao ChenQing Mu
Aug 24, 2010·ACS Medicinal Chemistry Letters·Robert C VaskoShelli R McAlpine
Jan 1, 2014·ACS Medicinal Chemistry Letters·Seong Jong KimShelli R McAlpine
Feb 24, 2012·Organic Letters·Erinprit K SinghShelli R McAlpine
Jul 4, 2013·Organic Letters·Chun-Chieh LinShelli R McAlpine
Oct 12, 2012·The Journal of Organic Chemistry·Hendra WahyudiShelli R McAlpine
Jul 23, 2014·ACS Medicinal Chemistry Letters·Yen Chin KoayShelli R McAlpine
Nov 14, 2014·Organic Letters·N VasudevanD Srinivasa Reddy

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