Synthesis and Evaluation of New Antimalarial Phenylurenyl Chalcone Derivatives

Abstract

Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3'-N-(N'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC(50) of 1.76 microM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms.

Synthèse et criblage antiplasmodial de quelques benzimidazolyl-chalcones

“…En effet, les chalcones posséderaient de bonnes propriétés anti-infectieuses qui pourraient être mises à profit pour l'élaboration de médicaments antiviraux, antimicrobiens et antiparasitaires dont des médicaments antipaludiques (Jain et Triveti, 2010;Bijo et al, 2014). Les chalcones déploieraient leurs activités antiplasmodiales par des mécanismes différents de ceux connus à savoir l'inhibition de la cystéine protéase plasmodiale, l'inhibition de l'hydrolyse de la globine ou encore l'inhibition de la formation d'hémozoïne (Dominguez et al, 2005). Quant au benzimidazole, du fait de son analogie structurale avec la purine, il constitue le noyau diaza-hétérocyclique de très nombreux médicaments notamment des médicaments anthelminthiques (Jacobs et Taylor, 2001).…”

Identification of Novel Phenyl Butenonyl C-Glycosides with Ureidyl and Sulfonamidyl Moieties as Antimalarial Agents

“…14,18 Phenyl urenyl chalcones also exhibit antimalrail activity via multiple mechanisms. 7 Inspired by the above facts we thought to design and synthesize compounds based on sugars having C-linked phenyl propenone moiety and diphenyl urea units together to get hitherto unreported antimalarial agents (Figure 1). In order to further analyze the feature requirement of these molecules in 3D space, we analyzed the common features through HipHop algorithm.…”

Chemical synthesis, docking studies and biological effects of functionalized 1,3-diaryl-2-propen-1-ones on human colon cancer cells

“…Chal-cones (1, 3-diaryl-2-propen-1-ones), constituting an enone system between two aromatic rings are an important class of natural products which are considered as precursors for various flavonoids and exhibit interesting pharmacological activities (Stu et al, 1971). Chalcones, originating from natural and synthetic routes possess several biological activities, such as cytotoxic (Modzelewska et al, 2006) anti-malarial (Dominguez et al, 2005), antileishmanial (Boeck et al, 2006) anti-inflammatory (Yang et al, 2007), anti-HIV (Cheenpracha et al, 2006), antifungal (Svetaz et al, 2004) and as tyrosine kinase inhibitors (Neryr et al, 2004). Because of very high pharmacological interest, these molecules have attracted medicinal chemists to design and synthesize further large number of chalcones with different functional groups.…”