A facile synthesis and discovery of highly functionalized tetrahydro-pyridines and pyridines as antimycobacterial agents.
The four-component reaction of ethyl-3-oxo-4-(arylsulfanyl)butanoate, substituted aromatic aldehydes and ammonium acetate afforded novel ethyl 4-hydroxy-2,6-diaryl-5-(arylsulfanyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylates. These tetrahydro-pyridine esters upon dehydrogenation with dichlorodicyanobenzoquinone (DDQ) afforded highly functionalized pyridines in excellent yields. These novel heterocycles were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv using agar dilution method. Among the compounds screened, ethyl 2,6-di(2-bromophenyl)-4-hydroxy-5-(phenylsulfanyl)-3-pyridinecarboxylate was found to be the most active with a minimum inhibitory concentration of 1.33 microM against Mycobacterium tuberculosis and is 5.74 and 38.17 times more potent than the first line anti-tuberculosis (TB) drugs, ethambutol and pyrazinamide respectively.
Raju
Suresh Kumar
SK
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India.
Stephen
Michael Rajesh
MR
Subbu
Perumal
P
Debjani
Banerjee
B
Perumal
Yogeeswari
Y
Dharmarajan
Sriram
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004977:Ethambutol / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011725:Pyridines; C551752:ethyl 2,6-di(2-bromophenyl)-4-hydroxy-5-(phenylsulfanyl)-3-pyridinecarboxylate; D011718:Pyrazinamide; D004977:Ethambutol