HDAC and NF-κB mediated cytotoxicity induced by novel N-Chloro β-lactams and benzisoxazole derivatives

Novel N-chloro a-Lactam and benzisoxazole derivatives were successfully synthesized with excellent yields (92-96%) under simple and mild reaction conditions. The beta-lactams as a class acquired importance since the discovery of penicillin which contains beta-lactam unit as an essential structural feature of its molecule, this interest continued unabated because of the therapeutic importance of beta-lactam antibiotics. In silico studies of the compounds with cancer drug target enzymes showed the inhibition of HDAC (Histone Deacetylase) and NF-kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells) significantly. The compounds were then investigated for the inhibitory potential against the same enzymes in vitro. NF-kappa B inhibition was investigated by trans activation assay using HEK293/NF-kappa B-luc cells. Overall, the synthesized compounds induce the cancer cell toxicity by restraining the NF-kappa B transcription factor mediated by HDAC inhibition and thus the compounds act as dual inhibitors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.