Design synthesis and evaluation of some 1 azetidinonesubstituted 2 un substitutedbenz imidazole and or benztriazole derivatives for antimalarial activity

Abstract

Background: Malaria is an infectious disease affecting humans and animals caused by parasitic single celled microorganisms belonging to the plasmodium group. Malaria causes several symptoms fever, tiredness, vomiting and headaches. In severe cases it may cause yellow skin, seizures, coma or even death. So it is necessary to treat this disease in early stage. So many drugs example, Chloroquine, Pamaquine, Primaquine, Mefloquine are available in the market that act as antimalarial agents. newlineAim: In most of areas of Southeast Asia, drug resistance has been developed. Chloroquine resistant P. falciparum and artemisinin resistant P. falciparum is a major problem now days. So, it is necessary to develop potential antimalarial agents. Benzimidazole and benztriazole nucleus has almost structure similarity with quinoline moiety. Benzimidazole is a wellknown pharmacophore that has a largest medicinal value including anticancer, antifungal, anthemintic, antibacterial like activity. There is no any anti malarial drug in the market that contain benzimidazole or benztriazole nucleus. So based on this knowledge, several azetidinone substituted benzimidazole and benztriazole derivatives, that have structure similarity with chloroquine drug, was synthesized and evaluated for their antimalarial activity. newlineMaterials and Methods: Benzene-1,2-diamine, formic acid, ethylchloroacetate, anhydrous K2CO3, hydrazine hydrate, benzaldehyde, p-methoxybenzaldehyde, o-chlorobenzaldehyde, m-nitrobenzaldehyde, o-hydroxybenzaldehyde, o-nitrobenzaldehyde chloroacetylchloride, triethylamine, glacial acetic acid, methanol. Docking study was done to find the molecules that show better binding to the receptor. Synthesis of those molecules was done and in vitro antimalarial activity was performed newlineResults: Compound 2(d) was giving maximum whereas; compound 2(c) was giving minimum binding affinity. Compound 2(a) was showing maximum toxicity whereas; compound 1(a), 1(c), 1(d), 2(c), 3(c), 3(d) and 3(d) were showing moderate toxicity whereas; Compound 1(b), 1