by Keyword: Antiplasmodial
Fulgheri, F, Manca, ML, Fernàndez-Busquets, X, Manconi, M, (2023). Analysis of complementarities between nanomedicine and phytodrugs for the treatment of malarial infection Nanomedicine 18, 1681-1696
The use of nanocarriers in medicine, so-called nanomedicine, is one of the most innovative strategies for targeting drugs at the action site and increasing their activity index and effectiveness. Phytomedicine is the oldest traditional method used to treat human diseases and solve health problems. The recent literature on the treatment of malaria infections using nanodelivery systems and phytodrugs or supplements has been analyzed. For the first time, in the present review, a careful look at the considerable potential of nanomedicine in promoting phytotherapeutic efficacy was done, and its key role in addressing a translation through a significant reduction of the current burden of malaria in many parts of the world has been underlined.
JTD Keywords: antiplasmodial activity, bioavailability, chloroquine, combination therapy, discovery, drug-delivery, drug-delivery systems, nanocapsules, nanomedicine, natural molecules, pharmacokinetics, phytomedicine, plasmodium-falciparum, Artemisinin-based combination therapy, Drug-delivery systems, Nanomedicine, Natural molecules, Phytomedicine, Solid lipid nanoparticles
Quiliano, Miguel, Pabón, Adriana, Moles, Ernest, Bonilla-Ramirez, Leonardo, Fabing, Isabelle, Fong, Kim Y., Nieto-Aco, Diego A., Wright, David W., Pizarro, Juan C., Vettorazzi, Ariane, López de Cerain, Adela, Deharo, Eric, Fernàndez-Busquets, Xavier, Garavito, Giovanny, Aldana, Ignacio, Galiano, Silvia, (2018). Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery European Journal of Medicinal Chemistry 152, 489-514
Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70–73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70–73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50s < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC50s < 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.
JTD Keywords: Antiplasmodial, Antimalarial, Arylamino alcohol, Multi-stage activity, Hsp90, Enantiomer separation
