Design, Synthesis, In Silico Molecular Docking, ADMET Studies, and Biological Evaluation of Novel Substituted Diphenyl Pyrazole Incorporated 1,2,3-Triazolyl Benzene Sulfonamides

Abstract Objective: A novel triazolyl benzene sulfonamides were synthesized and evaluated for antitubercular and anticancer activity. Methods: Our study is dedicated to preparing highly efficient diphenyl pyrazole triazolyl benzene sulphonamides, as part of our ongoing efforts in the development of effective antitubercular and anticancer agents. The antitubercular activity was performed against the M. tuberculosis H37RV strain using a Microplate Alamar Blue Assay (MABA). The in silico pharmacokinetic profile (ADMET) and molecular docking studies were conducted using the enzyme crystal structure of Burkholderia cenocepacia dihydropteroate synthase complexed with 7,8-dihydropteroate (PDBID:2Y5S) and DHFR from Bacillus stearothermophilus (PDB ID: 1ZDR). Results and Discussion: The synthesis of eighteen novel derivatives was followed by the characterization, antitubercular, and anticancer screening of those compounds. Physical (MP and TLC) and spectral (FT-IR, 1H NMR, and MS) approaches were used to characterize the compounds. The H37RV strain was tested for antitubercular activity using the Microplate Alamar Blue Assay (MABA) method. When tested for antitubercular activity, compounds (Va), (Ve), and (VIIe) showed substantial activity at 50 µg/mL concentrations, whereas other substances showed action at 100 µg/mL concentrations. The compounds (Va), (Ve), and (VIIe) exhibit promising binding scores with DHTP and DHFR, which contributes to their efficacy as anticancer agents. The ADMET results have a positive impact on the effectiveness of the compounds. The same compounds have also demonstrated good results in the MTT assay ranging between 2 to 10 µg/mL, out of which (Va) showed strong cytotoxic activity of 1.73 µg/mL. Conclusions: The compounds were synthesized in quantitative yields and possessed antitubercular activity and anticancer activity.