Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance.

ABSTRACT: COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal interaction properties of COTI-2 have not been investigated in detail so far. This is unexpected, as we have recently shown that COTI-2 forms stable ternary complexes with copper and glutathione, which renders this drug a substrate for the resistance efflux transporter ABCC1. Herein, the complex formation of COTI-2, two novel terminal N-disubstituted derivatives (COTI-NMe₂ and COTI-NMeCy), and the non-substituted analogue (COTI-NH₂) with iron, copper, and zinc ions was characterized i

SUBMITTER: Posa V 

PROVIDER: S-EPMC9497102 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature