Open AccessCyto-genotoxicity assessment of potential anti-tubercular drug candidate Molecule-trans-cyclohexane-1, 4-Diamine derivative-9u in human lung epithelial cells A549
Author(s) -
Ekta Kapoor,
Vinay Tripathi,
Vivek Kumar,
Vijay Juyal,
Sunita Bhagat,
Veerma Ram
Publication year - 2014
Publication title -
toxicology international/indian journal of toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.129
H-Index - 26
eISSN - 0976-5131
pISSN - 0971-6580
DOI - 10.4103/0971-6580.128800
Subject(s) - genotoxicity , cytotoxicity , ethambutol , mycobacterium tuberculosis , chemistry , tuberculosis , pharmacology , microbiology and biotechnology , biology , medicine , in vitro , biochemistry , toxicity , pathology , organic chemistry
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.