Discovery of new antitubercular oxazolyl thiosemicarbazones.
Twenty 4-(5-cyclobutyloxazol-2-yl)thiosemicarbazones were synthesized and evaluated for preliminary in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB) and multidrug-resistant Mycobacterium tuberculosis (MDR-TB). Among them, (4-bromophenyl)(phenyl)methanone N-(5-cyclobutyl-1,3-oxazol-2-yl)thiosemicarbazone 6q was found to be the most active compound in vitro with minimum inhibitory concentration of 0.05 microg/mL against MTB and MDR-TB. In the in vivo animal model 6q decreased the bacterial load in lung and spleen tissues with 2.1 log 10 and 3.72 log 10 protections, respectively, at 50 mg/kg body weight dose.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani-333031, India. dsriram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Thirumurugan
Rathinasababathy
R
Pavana
Roheet Kumar
RK
D000904:Antibiotics, Antitubercular / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C512072:(4-bromophenyl)(phenyl)methanone N-(5-cyclobutyl-1,3-oxazol-2-yl)thiosemicarbazone; D000904:Antibiotics, Antitubercular; D013882:Thiosemicarbazones