Sen, Tejosmita; Neog, Kashmiri; Sarma, Sangita; Manna, Prasenjit; Deka Boruah, Hari Prasanna; Gogoi, Pranjal; Singh, Anil Kumar published the artcile< Efflux pump inhibition by 11H-pyrido[2,1-b]quinazolin-11-one analogues in mycobacteria>, Name: 3-Chloro-2-fluorobenzonitrile, the main research area is pyrido quinazolinone analog preparation efflux pump mycobacteria tuberculosis; Efflux pump; Efflux pump inhibitor; Fluoroquinolone resistance; Mycobacterium; Quinazolinone.
Mycobacterium tuberculosis infection causes 1.8 million deaths worldwide, of which half a million has been diagnosed with resistant tuberculosis (TB). Emergence of multi drug resistant and extensive drug resistant strains has made all the existing anti-TB therapy futile. The major involvement of efflux pump in drug resistance has made it a direct approach for therapeutic exploration against resistant M. tuberculosis. This study demarcates the role of 11H-pyrido[2,1-b]quinazolin-11-one (quinazolinone) analogs as efflux pump inhibitor in Mycobacterium smegmatis. Sixteen quinazolinone analogs were synthesized by treating 2-aminopyridine and 2-fluorobenzonitrile with KtOBu. Analogs were tested, and 3a, 3b, 3c, 3g, 3j, 3l, 3m, and 3p were found to modulate EtBr MIC by >4 whereas 3a, 3g, 3i and 3o showed >4 modulation on norfloxacin MIC. 3l and 3o in addition to their very low toxicity they showed high EtBr and norfloxacin accumulation resp. Time kill curve showed effective log reduction in colony forming unit in presence of these analogs, thus confirming their role as efflux pump inhibitor. Through docking and alignment studies, we have also shown that the LfrA amino acid residues that the analogs are interacting with are present in Rv2333c and Rv2846c of M. tuberculosis. This study have shown for the first time the possibility of developing the 11H-pyrido[2,1-b]quinazolin-11-one analogs as efflux pump inhibitors for M. smegmatis and hence unbolts the scope to advance this study against resistant M. tuberculosis as well.
Bioorganic & Medicinal Chemistry published new progress about Efflux pump inhibitors. 94087-40-8 belongs to class nitriles-buliding-blocks, and the molecular formula is C7H3ClFN, Name: 3-Chloro-2-fluorobenzonitrile.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts