Synthesis of pyrazinamide Mannich bases and its antitubercular properties.
A series of pyrazinamide (PAZ) Mannich bases has been synthesized by reacting PAZ, formaldehyde, and various substituted piperazines using microwave irradiation with the yield ranging from 46% to 86%. The synthesized compounds were evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB). Among the synthesized compounds, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-4-((pyrazine-2-carboxamido)methyl)piperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (17) was found to be the most active compound in vitro with MIC of 0.39 and 0.2 microg/mL against MTB and multidrug-resistant MTB, respectively. In the in vivo animal model 17 decreased the bacterial load in lung and spleen tissues with 1.86 and 1.66-log10 protections, respectively.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India. dsriram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Reddy
Sushma Pobba
SP
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000138:chemical synthesis; D013154:Spleen / Q000378:metabolism
D000995:Antitubercular Agents; D008352:Mannich Bases; D011718:Pyrazinamide