Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents

Dalton Transactions : an International Journal of Inorganic Chemistry
Victoria ObermoserRonald Gust

Abstract

[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), an organometallic derivative of the irreversible cyclooxygenase-1/2 (COX-1/2) inhibitor acetylsalicylic acid (ASS), demonstrated high growth-inhibitory potential against various tumor cell lines and inhibition of both COX isoenzymes. With the objective of increasing the selectivity for COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 of the ASS moiety, respectively. Increased COX-2 selectivity is desirable as this isoenzyme is predominantly related to the development of cancer and abnormal tissue growth. The new compounds were investigated in comprehensive cellular biological assays to identify the impact of the chlorine substitution at the complex on COX-1/2 inhibition, antiproliferative activity, apoptosis, metabolic activity, cell-based COX inhibition, and cellular uptake. Chlorination distinctly reduced the effects at isolated COX-1 (about 25% inhibition at 10 μM; Co-ASS: 82.7%), while those at COX-2 remained almost unchanged (about 65% inhibition at 10 μM; Co-ASS: 78.5%). In cellular systems, with exception of the 6-Cl derivative, all compounds showed notable antitumor activity in COX-1/2 expressing tumor cells (HT-29 (IC50 = 1.5-2.7 μM), ...Continue Reading

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Citations

Oct 21, 2018·Journal of Cellular Physiology·Nasser Hashemi GoradelKeywan Mortezaee
May 8, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Sirui LiBin Liu
Oct 17, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Daniel BaeckerRonald Gust
Jul 31, 2021·Biological Trace Element Research·Kangping LiuJianzhu Liu
Nov 30, 2018·Chemical Reviews·Bernhard EnglingerWalter Berger

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Methods Mentioned

BETA
acetylation
atomic absorption
column chromatography
Assay

Software Mentioned

Lightcycler®96
NCSS
Prism

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