Emergence of pyrido quinoxalines as new family of antimalarial agents

• Published in: European journal of medicinal chemistry 2014-04, Vol.77, p.280-287
• Main Authors: Chandra Shekhar, A., Shanthan Rao, P., Narsaiah, B., Allanki, Aparna Devi, Sijwali, Puran Singh
• Format: Article
• Language: English
• Subjects: Antimalarial activity; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Dose-Response Relationship, Drug; Erythrocytes - drug effects; Erythrocytes - microbiology; Gould–Jacobs reaction; Humans; Molecular Structure; Plasmodium falciparum; Plasmodium falciparum - drug effects; Pyrazines - chemical synthesis; Pyrazines - chemistry; Pyrazines - pharmacology; Pyrido quinoxaline; Quinolones; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.03.010

A series of novel N-alkyl dihydro pyrido quinoxaline derivatives were synthesized using Gould–Jacobs reaction and evaluated their antimalarial activity in vitro against chloroquine sensitive (3D7) and drug resistant (Dd2) strains of Plasmodium falciparum. Among the compounds tested, 10 compounds were more potent than their structural standard analog ciprofloxacin, including 2 derivatives 5e and 5h, which showed 3.3–7.4 times more potency than ciprofloxacin against both the parasite strains. The results are encouraging and a lead molecule may emerge which is useful alone or in combination therapy. A series of novel (28) pyrido quinoxaline derivatives were synthesized and evaluated for antimalarial activity against the human malaria parasite Plasmodium falciparum. Some of the derivatives were more potent than ciprofloxacin, including the compound 5h shown below. [Display omitted] •A convenient method to synthesize pyrido quinoxaline derivatives from quinoxaline-6-amine by Gould–Jacobs reaction.•Assessment of novel pyrido quinoxaline molecules for antimalarial activity.•Identified 10 compounds with more potency than ciprofloxacin.•Compounds 5e and 5h seem to be attractive candidates for optimization to achieve better potency.•All the potent compounds showed similar activity against both chloroquine sensitive and resistant strains.