Structure–Activity relationships of novel anti-malarial agents. Part 6: N-(4-Arylpropionylamino-3-benzoylphenyl)-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides

Abstract

We have demonstrated that the p-trifluoromethylphenylpropionylamino residue at the 2-position of the core structure leads to an active benzophenone-type anti-malarial agent. The attempt to improve water solubility by introduction of an amino group into the alpha-position of the arylpropionyl residue resulted in decreased activity.

Structure-Based Drug Discovery for Tropical Diseases

“…Peptidomimetic compounds with a benzophenone core were identified as promising lead compounds. Subsequently, several cycles of lead optimization led to development of compounds with enhanced inhibitory potency capable of suppressing the growth of the multiresistant P. falciparum in the nanomolar range [135][136][137][138][139]. However, when tested against a murine malaria model the inhibitors were inactive.…”

Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity

“…The action of ArNO 2 against the malaria parasite P. falciparum received relatively little attention, although a number of nitrofurans, nitrobenzenes, nitroimidazoles, and 4-nitrobenzothiadiazole were shown to possess in vitro antiplasmodial activity at micromolar or lower concentrations [17,195,305,306]. The antiplasmodial activity of a series of nitrobenzenes and nitrofurans increases with their E 1 7 , log D, and their efficiency of inhibition of P. falciparum glutathione reductase (Pf GR) [195].…”

Synthesis of Acrylic Acid Derivatives: A Fast, Multigram Scale Methodology via Ultrasound Irradiation / Obtenção de Derivados de Ácidos Acrílicos: Uma Metodologia Rápida, em Escala Multigrama, por Irradiação de Ultrassom

“…Acrylic acids derivatives, in special cinnamic acid analogs, have a wide range of applications such as in cosmetics chemistry [1] , in medicinal chemistry: as potential new entities against schistosomiasis, tuberculosis, malaria, cancer, and others [2][3][4][5][6] , in polymer chemistry and food chemistry [7,8] . In spite of the great variety of protocols available for the synthesis of these substances [9][10][11][12] , the search for novel methodologies applicable to the multigram scale synthesis of acrylic acids is still an ongoing field.…”