Synthesis and Evaluation of Antiparasitic Activities of New 4-[5-(4-Phenoxyphenyl)-2H-pyrazol-3-yl]morpholine Derivatives

Abstract

A series of new 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine derivatives, prepared by two synthetic routes, were in vitro assayed against three Trypanosoma strains, Leishmania donovani, and Plasmodium falciparum K1. Seven out of 17 compounds showed moderate to very good activity against blood stage T. b. rhodesiense, with 10 and 17 exhibiting highest potency (IC50 of 1.0 and 1.1 microM, respectively). Interestingly, the beta-diketone precursors 1-3 had good antitrypanosomal activity toward the insect stage, with IC50 values of 1.0-3.4 microM. Among different compounds with moderate activity against T. cruzi, compound 17 showed the lowest IC50 value of 9.5 microM; thus, the series seemed to act selectively toward the different Trypanosoma parasites. Eight compounds were moderately active against L. donovani, with 2, 3, and 12 being the most promising ones (IC50 values of 2.3-5.2 microM), whereas compound 14 was the only derivative with good activity against P. falciparum (IC50 of 3.7 microM).

Synthesis, Characterization and Biological Evaluation of Some Benzothiazole Derivatives as Potential Antimicrobial Agent.

“…In addition, a large number of thiophene derivatives have found to exhibit pharmacological activity [32][33][34] . Furthermore, diverse chemotherapeutic activities have ascribed to pyrazoles as antimicrobial [35][36] , antiparasitic 37 , antivirial 38 , and antineoplastic agents [39][40][41][42] . A detail literature survey indicates that benzothiazole ring system have a unique position in the designing and synthesis of novel biological active agents with remarkable analgesic and anti-inflammatory activities.The preliminary study of the structure-activity relationship reveals that electronic factors in benzothiazole ring has a great effect on a antimicrobial activity of these compounds.…”

Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives

“…Furthermore, most of compounds prepared from 3-acetyl coumarin have anti-microbial, anti-inflammatory and antioxidant activities [6][7][8][9][10] . The heterocyclic systems encompassing pyrazoles are explored to the maximum extent owing to their wide spectrum of pharmacological activities, such as analgesic, anti-inflammatory, antipyretic, anti-depressant, hypotensive, anti-cancer, antibacterial, anti-parasitic, and anti-androgenic agents [10][11][12][13][14][15][16][17] . Special attention is warranted towards the synthetic design and development of pyrazoles because of their high demand in academic and pharmaceutical sectors, and in continuation of our previous work in the synthesis of biologically active heterocycles 6,10 we report herein synthesis of some new 3-[3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl]-2H-chromen-2-one 4a-k, for investigation of their antibacterial profile.…”

Synthesis and preliminary evaluation of brominated 5-methyl-2,4-dihydropyrazol-3-one and its derivatives as cytotoxic agents

“…The chemistry of pyrazolone and its derivatives is particularly interesting because of their potential application in medicinal chemistry as analgesic (GÜrsoy et al, 2000;Amir et al, 2008), anti-inflammatory (Satyanarayana and Rao, 1995), antipyretic (Manna et al, 1992), antiparasitic (Kuettel et al, 2007), antimalarial (Kativar et al, 2005), antifungal (Bekhit and Fahmy, 2003) and enzyme inhibitory agents (Regan et al, 2003;Li et al, 2004 andDolle et al, 1994). As an example, edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, 1a) has been recently shown to produce marked attenuation of brain damage caused by ischemia-reperfusion (Anzai et al, 2004) and its pharmacological actions were attributed to its antioxidant activity, as a potent hydroxyl radical scavenger (Parmar et al, 1999).…”