Structure–Activity Relationship Studies and Plasmodium Life Cycle Profiling Identifies Pan-Active N-Aryl-3-trifluoromethyl Pyrido[1,2-a]benzimidazoles Which Are Efficacious in an in Vivo Mouse Model of Malaria

Abstract

Structure-activity relationship studies and Plasmodium life cycle profiling identifies panactive N-aryl-3-trifluoromethyl pyrido[1,2a]benzimidazoles which are efficacious in an in vivo mouse model of malaria.

Benzimidazole Derivatives Are Potent against Multiple Life Cycle Stages of Plasmodium falciparum Malaria Parasites

“…All other compounds have been described before. 6,10,22,23,25 Ethical Clearance. The in vitro work described holds ethics approval from the University of Pretoria (Health Sciences (506/2018) and Natural Sciences (180000094) Ethics Committee and the University of the Witwatersrand Human Research Ethics Committee (M130569) and Animal Ethics Committee (20190701−7O).…”

“…4,5 Aside from the many benzimidazole-based drugs in current clinical use, antimalarial benzimidazole agents have been reported in the literature. 6−13 Relatedly, pyrido[1,2-a]benzimidazole (PBI) derivatives have demonstrated broad-spectrum biological properties 14−20 antischistosomal 22,24,25 activities of these fused heterocyclic compounds.…”

“…The detailed structural modifications within this chemical space have been previously described. 13,22,23,25 Meanwhile, the chemical and spectroscopic information on three previously unreported PBI analogues are presented in Supporting Information 1. Compounds were screened for activity against ABS, early stage and late-stage gametocytes, male gametes, and oocysts in mosquitoes with several compounds displaying activity across multiple stages of P. falciparum parasites in vitro (Figure S1).…”

Simple inorganic base promoted polycyclic construction using mucohalic acid as a C3 synthon: synthesis and AIE probe application of benzo[4,5]imidazo[1,2-a]pyridines

“…Among them, N-heterocycles as typical molecular frameworks of synthetic drugs, natural products, agrochemicals and functional materials, are widely used in organic synthetic chemistry. 1 For example, benzo[4,5]imidazo-[1,2- a ]pyridines are not only a class of significant fluorescent material molecules, 2 but also have potential medicinal properties, such as antidiabetic, 3 anti-cancer, 4–6 anti-malarial, 7,8 antifungal, 9 antischistosomal, 10,11 etc . It is worth noting that benzo[4,5]imidazo[1,2- a ]-pyridines containing a C 1 –N bond have excellent biological activities (Fig.…”

Expanding the Activity Profile of Pyrido[1,2-a]benzimidazoles: Synthesis and Evaluation of Novel N1-1-Phenylethanamine Derivatives against Schistosoma mansoni

“…In this regard, we have previously reported on the antischistosomal properties , of pyrido­[1,2- a ]­benzimidazole (PBI) derivatives, which have broad-spectrum biological properties including analgesic, antipyretic, antibacterial, antiviral, antimicrobial, antifungal, antimalarial, − antimycobacterial, and antitumor , activities. A summary of the structure–activity relationship (SAR) studies for first and second generation schistosomicidal PBI analogs exemplified by the most potent analogs G1 and G2 is presented in Figure .…”