Synthesis and in Vitro Antiprotozoal Activity of Bisbenzofuran Cations

Abstract

Forty three cationic bisbenzofurans were synthesized either by interaction of o-hydroxyaldehydes with alpha-halogenated ketones followed by intramolecular ring closure or by a copper- or palladium-mediated heteroannulation of substituted o-iodophenols with terminal acetylenes. In vitro antiprotozoal activities of compounds 1-43 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicity against mammalian cells were influenced by the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. One bisamidine displayed an antitrypanosomal efficacy comparable to that of pentamidine and melarsoprol. Twenty two compounds were more potent than pentamidine and seven dications were more effective than artemisinin against P. falciparum. Eight bisbenzofurans displayed activity against L. donovani superior to that of pentamidine. Overall, bisamidines connected by two-carbon linkers exhibited the highest efficacies against T. b. rhodesiense, P. falciparum, and L. donovani.

Structure-Based Drug Discovery for Tropical Diseases

“…A start point to tackle these issues is the molecular manipulation of known drugs or active classes of compound to generate new scaffolds with improved potency, safety or straightforward synthesis. Currently, analogues of existing antiparasitic drugs are under investigation for a variety of neglected diseases [28][29][30][31][32][33][34][35][36][37].…”

Synthesis, Characterization, and Antibacterial Activity of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) Complexes of Schiff's Base Type Ligands Containing Benzofuran Moiety

“…Among them, benzofuran based fused heterocycles have been of great interest as they are abundant in nature and have wide pharmacological activities [8]. Benzofuran based compounds have been reported to show activities as anti-infective agents, like antifungal [9][10][11][12], antiprotozoal, and antitubercular [13][14][15], and also in the treatment of antiarrhythmic [16] and cardiovascular [17] diseases. According to the literature survey in the recent years, there has been an increased interest investigation of anti-microbacterial activities on benzofuran derivatives, especially 2-substituted [18] or 2,3-disubstituted benzofurans derivatives [19].…”

Synthesis and Antiprotozoal Properties of Pentamidine Congeners Bearing the Benzofuran Motif

“…8 Synthesis of isomeric 1-ethynyl-3-methoxybenzene 51 and 1-ethynyl-4-methoxybenzene 52 was carried out following the literature procedure. 10 The synthesis of the benzofurans 59-62 is outlined in Scheme 1.…”