Synthesis, biology, computational studies and in vitro controlled release of new isoniazid-based adamantane derivatives

Aim: There is a necessity for new drugs to be more efficient than today's standard due to the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) Results/methodology: 12 new isoniazid-based adamantane derivatives were synthesized and tested for their antitubercular activity. The pharmacological test results and the aqueous dissolution profile of representative examples of the new molecules are in agreement with the computational results obtained from docking poses and molecular dynamics simulations on the tested compounds. Conclusion: Among their congeners, the adamantane isonicotinoyl hydrazones Ia and Ih exhibit the best antitubercular activity (MIC = 0.04 mu g/ml) and the lowest cytotoxicity (selectivity index >= 2500). These results are useful for in future in vivo studies.