Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities
Year: 2015
Type: article
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.
Source: Journal of Medicinal Chemistry
Authors: Derek C. Medellin, Qiong Zhou, Robert Scott, R. Matthew Hill, Sarah K. Frail, Ramesh Dasari, Steven J. Ontiveros, Stephen C. Pelly, Willem A. L. van Otterlo, Tania Betancourt, Charles B. Shuster, Ernest Hamel, Ruoli Bai, Daniel V. LaBarbera, Snezna Rogelj, Liliya V. Frolova, Alexander Kornienko
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: U.S. Department of Defense, Welch Foundation, Texas Emerging Technology Fund, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, Division of Chemistry, Eunice Kennedy Shriver National Institute of Child Health and Human Development, DOD Peer Reviewed Cancer Research Program
Awards: NOVEL ANTI-METASTATIC AGENTS FOR THE TREATMENT OF DRUG-RESISTANT AND METASTATIC COLON CANCER, G380793897, G4744606257, Mode of Action of the Amaryllidaceae Alkaloid Lycorine-Promising Anticancer Agent, G7275631438, Mob1 Localization and Function During Mitosis, New Mexico IDeA Networks of Biomedical Research Excellence (INBRE)
OpenAlex ID: W2190066948