Cyto‑genotoxicity Assessment of Potential Anti‑tubercular Drug Candidate Molecule‑trans‑cyclohexane‑1, 4‑diamine Derivative‑9u in Human Lung Epithelial Cells A549

Increasing incidences of multiple drug‑resistance (MDR) in Mycobacterium tuberculosis are emerging as one among the serious public health threats and socio‑economic burden to the third world countries including India. Last couples of decades are witnesses of the dedicated and sustained efforts made toward the development of target specific and cost‑effective antimicrobial agents against MDR‑M. tuberculosis. However, the drugs in use are still incapable of controlling the upsurge of MDR. Thus, in order to address the issue, we synthesized a library of symmetrical trans‑cyclohexane‑1, 4‑diamine derivatives and evaluated their anti‑mycobacterium activity in H37RV strain of M. tuberculosis. A range of efficacy has been recorded in different derivatives of synthesized compounds and compound “9u” having i‑propyl group substitution at p‑position, was found to have more significant detrimental effects against the tested strain of M. tuberculosis. The present investigations were aimed to study whether the effective anti‑mycobacterium concentrations of “9u” are biologically safe to human cells or not? The human lung epithelial cell line‑A549 were exposed to a range of concentrations, i.e., at and above the anti‑mycobacterium effective dose of “9u” for a period of 0‑96 h. The standard endpoints of cytotoxicity viz., tetrazolium bromide salt (3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5‑diphenyl tetrazolium bromide), neutral red uptake, lactate dehydrogenase release, trypan blue dye exclusion assays; and genotoxicity viz., micronucleus and chromosomal aberrations assays were used to evaluate the bio‑safety of test compound. The compound “9u” shows no significant cytotoxicity and genotoxicity in A549 cells exposed to 10 − 5 M for 72 h, a concentration substantially higher than the concentration kill the H37Rv strain of M. tuberculosis. The compound 9u was found to be safe up to 10 − 4 M if given for 24 h. The data reveal the therapeutic potential of compound 9u against M. tuberculosis without any having any cytotoxicity and genotoxicity responses.