New Methionine-based P-toluenesulphonamoyl Carboxamide Derivatives as Antimicrobial and Antioxidant Agents: Design, Synthesis and Molecular Docking

Aim: The reported emergence of drug resistant microbes and the prevalence of oxidative stress related diseases prompted the need for the development of new antimicrobial and antioxidant agents. The synthesis of methione-based sulphonamoyl carboxamides bearing aniline, pyridine and pyrimidine pharmacophores is reported.

Place and duration: Department of Industrial Chemistry, Renaissance University, Ugbawka, Enugu, 2018.

Methodology: The p-toluenesulphonyl chloride reaction with methionine gave compound 3a which was acylated to afford compound 3b. Further chlorination and aminolysis of compound 3b gave the carboxamide (3c). Nickel catalysed reaction of the carboxamide with aryl/heteroaryl halides afforded compounds 3d-f in excellent yields. Characterization of compounds was done using H1-NMR, C13-NMR, FTIR and elemental analysis. Their antimicrobial, antioxidant activity and molecular docking were determined.

Results: Compounds 3a and 3e had the best antimicrobial activity with minimum inhibitory concentration (MIC) in the range of 0.6 – 0.9mg/ml and the highest antioxidant percentage inhibition (93.53% and 93.28% at 200µg/ml respectively) comparable with ascorbic acid (96.83% at 200µg/ml) and also the best IC50 values of 1.031 and 1.051µg/ml.

The molecular docking study, revealed that compounds 3a (TPSA = 83.47 Å2) could permeate blood-brain barriers. Compound 3e (-11.14 kcal/mol) had a better in silico antibacterial activity than penicillin (-10.89 kcal/mol) while compound 3a (-14.90kcal/mol) had a better antioxidant activity than α-tocopherol (-14.82 kcal/mol).

Conclusion: All the synthesized compounds were confirmed to be likely drugs and potential antimicrobial and antioxidant, agents.