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

•Synthesized the novel N-chloro β-lactams and benzisoxazole compounds with an excellent yields.•Cancer drug target enzymes showed significantly inhibitions on both HDAC and NFkB.•Developed compounds were not shown cytotoxicity against normal cells.•The results indicate that the compound could be used as a dual inhibitor for both HDAC and NFkB.

Novel N-chloro â-Lactam and benzisoxazole derivatives were successfully synthesized with excellent yields (92–96%) under simple and mild reaction conditions. The β-lactams as a class acquired importance since the discovery of penicillin which contains β-lactam unit as an essential structural feature of its molecule, this interest continued unabated because of the therapeutic importance of β-lactam antibiotics. In silico studies of the compounds with cancer drug target enzymes showed the inhibition of HDAC (Histone Deacetylase) and NF-κB (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-κB inhibition was investigated by trans activation assay using HEK293/NF-κB-luc cells. Overall, the synthesized compounds induce the cancer cell toxicity by restraining the NF-κB transcription factor mediated by HDAC inhibition and thus the compounds act as dual inhibitors.

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