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2,2′‐Bipyridine‐Modified Tamoxifen: A Versatile Vector for Molybdacarboranes
Author(s) -
Schwarze Benedikt,
Jelača Sanja,
Welcke Linda,
MaksimovićIvanić Danijela,
Mijatović Sanja,
HeyHawkins Evamarie
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900554
Subject(s) - chemistry , tamoxifen , stereochemistry , cytotoxic t cell , nitric oxide , ligand (biochemistry) , derivative (finance) , bipyridine , molecule , 2,2' bipyridine , cancer research , biochemistry , in vitro , cancer , receptor , biology , medicine , breast cancer , crystallography , organic chemistry , crystal structure , economics , financial economics
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‐MoC 2 B 9 H 11 ] 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‐κ 2 N , N ′}‐3‐(CO) 2 ‐ closo ‐3,1,2‐MoC 2 B 9 H 11 ] ( 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.