2,2′-Bipyridine-Modified Tamoxifen: A Versatile Vector for Molybdacarboranes

Abstract

Investigations on the antitumor activity of metallacarboranes are sparse in the literature and limited to a handful of ruthena- and molybdacarboranes. In this study, the molybdacarborane fragment [3-(CO)2-closo-3,1,2-MoC2B9H11] was combined with a vector molecule, inspired by the well-known drug tamoxifen or 4,4′-dihydroxytamoxifen (TAM-diOH). The molybdacarborane derivative [3,3-{4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine-κ2N,N′}-3-(CO)2-closo-3,1,2-MoC2B9H11] (10), as well as the ligand itself 4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (6) showed cytotoxic activities in the low micromolar range against breast adenocarcinoma (MDA-MB-231, MDA-MB-361 and MCF-7), human glioblastoma (LN-229) and human glioma (U-251) cell lines. In addition, compounds 6 and 10 were found to induce senescence and cytodestructive autophagy, lower ROS/RNS levels, but only the molybdacarborane 10 induced a strong increase of nitric oxide (NO) concentration in the MCF-7 cells.