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

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.

SUBMITTER: Medellin DC

PROVIDER: S-EPMC4950951 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Medellin Derek C DC Zhou Qiong Q Scott Robert R Hill R Matthew RM Frail Sarah K SK Dasari Ramesh R Ontiveros Steven J SJ Pelly Stephen C SC van Otterlo Willem A L WA Betancourt Tania T Shuster Charles B CB Hamel Ernest E Bai Ruoli R LaBarbera Daniel V DV Rogelj Snezna S Frolova Liliya V LV Kornienko Alexander A

Journal of medicinal chemistry 20151217 1

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 ...[more]

PMID: 26641132

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