6533b81ffe1ef96bd1277e14

RESEARCH PRODUCT

Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs

Alessandro AttanzioVirginia SpanòAnna CarbonePatrizia DianaAlessandra MontalbanoStella CascioferroGirolamo CirrincionePaola BarrajaLuisa TesoriereBarbara Parrino

subject

antiproliferative activitybis-indolyl alkaloidsIndolesStereochemistryPopulationPharmaceutical ScienceAntineoplastic AgentsAntiproliferative activity; Apoptosis; Bis-indolyl alkaloids; Marine alkaloids; Thiazolyl-indolesBis-indolyl alkaloid010402 general chemistry01 natural sciencesArticlechemistry.chemical_compoundCell Line TumorDrug DiscoveryHumansCytotoxic T cellThiazolyl-indoleThiazoleMode of actioneducationlcsh:QH301-705.5Pharmacology Toxicology and Pharmaceutics (miscellaneous)Antitumor activityIndole testeducation.field_of_study010405 organic chemistryChemistryCell CycleImidazolesapoptosisApoptosiHCT116 CellsSettore CHIM/08 - Chimica Farmaceutica0104 chemical sciencesThiazoleslcsh:Biology (General)BiochemistryApoptosisCell cultureMCF-7 Cellsmarine alkaloidsMarine alkaloidthiazolyl-indolesDrug Screening Assays Antitumormarine alkaloids; bis-indolyl alkaloids; thiazolyl-indoles; apoptosis; antiproliferative activity

description

New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode of action. Results showed that the three compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while not exerting necrotic effects. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 and S phases, accompanied by a concomitant percentage increase of cells in the G2/M phase, and appearance of a subG1-cell population.

yearjournalcountryeditionlanguage
2016-12-14Marine Drugs
https://doi.org/10.3390/md14120226