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.