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J Med Chem. 2016 Jan 14;59(1):480-5. doi: 10.1021/acs.jmedchem.5b01426. Epub 2015 Dec 17.

Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities.

Author information

1
Department of Chemistry and Biochemistry, Texas State University , San Marcos, Texas 78666, United States.
2
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
3
Departments of Chemistry and Biology, New Mexico Tech , Socorro, New Mexico 87801, United States.
4
Department of Biology, New Mexico State University , Las Cruces, New Mexico 88003, United States.
5
Department of Chemistry and Polymer Science, Stellenbosch University , Stellenbosch, Western Cape, South Africa.
6
Materials Science, Engineering, and Commercialization Program, Texas State University , San Marcos, Texas 78666, United States.
7
Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick National Laboratory of Cancer Research, National Institutes of Health, Frederick, Maryland 21702, United States.

Abstract

Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents.

PMID:
26641132
PMCID:
PMC4950951
DOI:
10.1021/acs.jmedchem.5b01426
[Indexed for MEDLINE]
Free PMC Article

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