Design, synthesis, and evaluation of activity against breast cancer cells of new naphthalene derivatives as potential sirtuin enzymes inhibitors

Abstract

Author(s): Hayjaa Mohessen Mosa, Ayad Abed Ali Al-Hamashi

Epigenetic modifications are potentially therapeutic targets because of their reversibility in somatic inheritability patterns. The sirtuin enzyme family is a Nicotinamide Adenine Dinucleotide (NAD+)-dependent histone deacetylase. Sirtuins have been associated with the pathogenesis of cancer due to their function in gene expression, making them an interesting therapeutic target. In the current study, several naphthalene-containing molecules were designed. The molecular docking Glide software from Schrodinger Inc. was used to evaluate the virtual interactions of the designed compounds with sirtuin enzymes. Compounds with acceptable docking scores were nominated for organic synthesis. The new naphthalene derivatives were synthesized and characterized via FTIR and NMR spectroscopy. A preliminary antiproliferative study over aggressive, poorly differentiated, and multi-treatment resistant triple negative receptor breast cancer cells (AMJ13) showed that compound Y4 has a significant cytotoxicity with an IC50 of 82.8 M, which was comparable to the vorinostat with an IC50 of 85.9 M. The ADMET study indicated that compound Y4 has acceptable pharmacokinetic properties and a drug-like profile.

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