DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
Navegar
2 resultados
Resultados da Pesquisa
Item From rational design to serendipity : discovery of novel thiosemicarbazones as potent trypanocidal compounds.(2022) Braga, Saulo Fehelberg Pinto; Santos, Viviane Corrêa; Vieira, Rafael Pinto; Silva, Elany Barbosa da; Monti, Ludovica; Krake, Susann Hannelore; Martinez, Pablo D. G.; Dias, Luiz Carlos; Caffrey, Conor R.; Siqueira Neto, Jair Lage de; Oliveira, Renata Barbosa de; Ferreira, Rafaela SalgadoChagas disease is a major public health problem caused by Trypanosoma cruzi, with an estimated 6–7 million people infected and 70 million at risk of infection. T. brucei gambiense and T. brucei rhodesiense are two subspecies of related parasites that cause human African trypanosomiasis, a neglected tropical disease with also millions of people at risk of infection. Pharmacotherapy for both diseases suffers from low efficacy, side effects, or drug resistance. Recently, we reported a noncovalent competitive inhibitor of cruzain (IC50 26 μM, Ki 3 μM) and TbrCatL (IC50 50 μM), two cysteine proteases considered promising drug targets for trypanosomiasis. Here, we describe the design and synthesis of derivatives of our lead compound. The new thiosemicarbazone derivatives showed potency in the nanomolar concentration range against the two enzymes, but they were later charac- terized as aggregators. Nevertheless, the thiosemicarbazone derivatives showed promising antiparasitic activities against T. b. brucei (EC50 13–49.7 μM) and T. cruzi (EC50 0.027–0.59 μM) under in vitro conditions. The most active thiosemicarbazone was 200-fold more potent than the current anti-chagasic drug, benznidazole, and showed a selectivity index of 370 versus myoblast cells. We have identified an excellent candidate for further optimization and in vivo studies.Item Purity determination of a new antifungal drug candidate using quantitative 1H NMR spectroscopy : method validation and comparison of calibration approaches.(2019) Franco, Pedro Henrique Cavalcanti; Braga, Saulo Fehelberg Pinto; Oliveira, Renata Barbosa de; César, Isabela da CostaQuantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we have applied qNMR, using both the internal standard and the electronic refer- ence to access in vivo concentrations 2 calibration methods, to assess the purity of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well‐ resolved signals of completely relaxed nuclei. The analytical method was vali- dated following current guidelines, demonstrating selectivity, linearity, accu- racy, precision, and robustness. The calibration approaches were statistically compared, and no significant difference was observed when comparing the obtained results and their dispersion in terms of relative standard deviation. The proposed qNMR method may, therefore, be used for both qualitative and quantitative assessments of RI76 in early drug development and for character- ization of this compound.