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

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.

• Authors: Katerina Otrubova, Gerald Lushington, David Vander Velde, Kathleen L McGuire, Shelli R McAlpine
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 3 Pg. 530-44 (Feb 14 2008) ISSN: 0022-2623 [Print] United States
• PMID: 18186604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Depsipeptides
• sansalvamide A

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy)
• Depsipeptides (chemical synthesis, chemistry, pharmacology)
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Humans
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Molecular Structure
• Structure-Activity Relationship