Design, Synthesis, and Cytotoxicity Evaluation of Sulfonamide Derivatives as Potential HDAC Inhibitors

Abstract

Histone deacetylase (HDAC) enzymes are interesting targets for developing new therapeutic molecules. New sulfonamide derivatives were designed via the implication of docking experiments using Glide software to validate the binding affinity with several HDAC enzymes. Molecules involving sulfonamide moiety exhibit acceptable binding scores and zinc chelation properties. Compounds with acceptable docking scores were nominated for the organic synthesis. The final compounds were synthesized through the amide coupling reaction followed by an amine alkylation reaction to afford final compounds IVa-d. The ADME properties were virtually assessed utilizing QikProp Schrodinger. The virtual ADME results indicated the drug-likeness properties of the final compounds with no major violation of the rule of five. The preliminary cytotoxic activity evaluation showing that compounds Iva and IVb killing colon cancer cells (LS-174T) in \(IC_{50}\) of 0.37 \(\mu\)M and 0.44 \(\mu\)M, respectively.