TY - JOUR
T1 - Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents
AU - Kar, Sidhartha S.
AU - Bhat, Varadaraj G.
AU - Rao, Praveen P.N.
AU - Shenoy, Vishnu P.
AU - Bairy, Indira
AU - Shenoy, G. Gautham
PY - 2016/7/18
Y1 - 2016/7/18
N2 - A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 μg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.
AB - A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 μg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.
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U2 - 10.2147/DDDT.S104037
DO - 10.2147/DDDT.S104037
M3 - Article
C2 - 27486307
AN - SCOPUS:84978764212
SN - 1177-8881
VL - 10
SP - 2299
EP - 2310
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -
