A novel thiophene-3-carboxamide analog of annonaceous acetogenin exhibits antitumor activity via inhibition of mitochondrial complex I.

ABSTRACT: Previously we synthesized JCI-20679, a novel thiophene-3-carboxamide analog of annonaceous acetogenins which have shown potent antitumor activity, with no serious side effects, in mouse xenograft models. In this study, we investigated the antitumor mechanism of JCI-20679. The growth inhibition profile (termed "fingerprint") of this agent across a panel of 39 human cancer cell lines (termed "JFCR39") was measured; this fingerprint was analyzed by the COMPARE algorithm utilizing the entire drug sensitivity database for the JFCR39 panel. The JCI-20679-specific fingerprint exhibited a high similarity to those of two antidiabetic biguanides and a natural rotenoid deguelin which were already known to be mitochondrial complex I inhibitors. In addition, the fingerprint exhibited by JCI-20679 was n

SUBMITTER: Akatsuka A 

PROVIDER: S-EPMC5242172 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature