title: Cyto-genotoxicity Assessment of Potential Anti-tubercular Drug Candidate Molecule-trans-cyclohexane-1, 4-diamine Derivative-9u in Human Lung Epithelial Cells A549.
abstract: 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.
authors.affiliation: Atma Ram Sanatan Dharma College, New Delhi, India.
authors.forename: Ekta
authors.initials: E
authors.lastname: Kapoor
authors.affiliation: Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Tripathi
authors.affiliation: Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, Kumaun University, Nainital, Uttarakhand, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Juyal
authors.affiliation: Atma Ram Sanatan Dharma College, New Delhi, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Bhagat
authors.affiliation: Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, Dehradun, Uttarakhand, India.
authors.forename: Veerma
authors.initials: V
authors.lastname: Ram
keywords: A549 cell line; Mycobacterium tuberculosis; chromosomal aberration; cytotoxicity; micronucleus assay
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