Synthesis, leptospirocidal activity and QSAR analysis of novel quinoxaline derivatives.
A simple and efficient method has been developed for the synthesis of series of N-Mannich bases of (E)-3- (phenylimino/4-chlorophenylimino)-2,3-dihydro-1-[(N-substituted piperazinyl) methyl]quinoxaline-2-(1H)-one 3a-f and 4a-f. The requisite 2a and 2b were obtained by reaction between quinoxaline-2,3-dione 1 and aniline/p-chloroaniline. These compounds underwent NMannich reaction with various substituted piperazines to yield (title compounds 3a-f and 4a-f respectively. Structures of synthesized compounds were confirmed by spectral studies (IR, 1H NMR, 13C NMR and Mass) and elemental analysis. All the synthesized compounds were screened for in vitro leptospirocidal activty against Leptospira interrogans. The potent compounds 4a, 4b and 4c which showed maximum activity during in vitro studies were subjected to in vivo studies. The inhibitory activity of enzymes carboxypeptidase and transpeptidase, in leptospirosis by the synthesized compounds were determined. 3D-QSAR studies model developed showed the need for more hydrophobic and less steric groups as substituent groups to enhance the in vitro activity.
Department of Pharmaceutical Technology, Anna University of Technology Tiruchirapalli, Tiruchirapalli-620024, Tamilnadu, India.
Ayarivan
A
Puratchikody
Ramalakshmi
R
Natarajan
Mukesh
M
Doble
Shanmugam Hema
SH
Iswarya
Raj
R
Vijayabharathi
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D060326:Chemistry Techniques, Synthetic; D005260:Female; D007921:Leptospira interrogans / Q000187:drug effects*; D051379:Mice; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000900:Anti-Bacterial Agents; D011810:Quinoxalines; D010458:Peptidyl Transferases; D002268:Carboxypeptidases