Design, synthesis, characterization and in vitro, in vivo and in silico antimicrobial and antiinflammatory activities of a new series of sulphonamide and carbamate derivatives of a nebivolol intermediate

A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, (1)H & (13)C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.