Biotransformation of digitoxigenin by Cochliobolus lunatus

The biotransformation of digitoxigenin (1) by Cochliobolus lunatus was investigated. The biotransformation reaction was carried out in a 4-day process, resulting in the isolation of four products, whose structures were elucidated as 1beta-hydroxydigitoxigenin (2), 7beta-hydroxydigitoxigenin (3), 8beta-hydroxydigitoxigenin (4) and digitoxigenone (5). The production of these derivatives under the employed conditions has never been described so far. This is also the first report on the production of compound 4 by a biotransformation reaction

Molecular modeling study of complexes between ferriprotoporphyrin IX and antimalarial 4-quinolinecarbinolamines: a proposal of pharmacophore

Quinine and quinidine are well-known 4-quinolinecarbinolamines that exhibit antimalarial activity, but, in contrast, their epimers 9-epiquinine and 9-epiquinidine are almost inactive. Literature data are conflicting in describing the 4-quinolinecarbinolamine interaction mode with the molecular target, the ferriprotoporphyrin IX [Fe(III)PPIX]. In the present paper, a pharmacophore is proposed based on the binding of the non-aromatic nitrogen to the iron atom. The 4-quinolinecarbinolamine antimalarials were superimposed on the pharmacophore under consideration and complexes with Fe(III)PPIX were constructed. Conformational analyses of the complexes were performed applying the MM+ molecular mechanics method. The analysis of the complexes showed that the proposed ligand mode is possible although it does not explain the activity differences between epimers. A discussion of the structural aspects is also provided.

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro

A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation

Leishmanicidal plants from Brazilian Amazonia: a review

Made available in DSpace on 2017-06-02T11:14:54Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 9.pdf: 850332 bytes, checksum: 056660b15fbdd44b11d964f2a8a4a936 (MD5) Previous issue date: 23Universidade Federal do Pará. Programa de Pós-Graduação em Ciências Farmacêuticas. Belém, PA, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Ciências Farmacêuticas. Belém, PA, Brasil / Universidade Federal de Minas Gerais. Faculdade de Farmácia. Belo Horizonte, MG, Brasil.As leishmanioses constituem grave problema de saúde pública, ocorrendo em 98 países. O Brasil é responsável pela, quase, totalidade dos casos notificados de Leishmaniose Visceral (LV) nas Américas, e a doença está em processo de urbanização. A Leishmaniose Tegumentar (LT) também apresenta ampla distribuição mundial. No Brasil, a região Norte possui o maior número de casos confirmados, a maioria deles causados por Leishmania (L.) amazonensis. Os fármacos de primeira escolha para o tratamento das leishmanioses são derivados do antimônio pentavalente (Sb5+), como o glucantime, o mais utilizado no Brasil. Fármacos antimoniais apresentam vários efeitos adversos, além disso, nos últimos anos, o problema agravou com o surgimento de resistência dos parasitos a estes medicamentos. A necessidade de novos fármacos leishmanicidas eficazes vem despertando o interesse em pesquisas de plantas utilizadas para este fim em países endêmicos, levando ao reconhecimento de produtos naturais ativos, os quais podem representar marcadores químico-biológicos para o desenvolvimento de fitoterápicos eficazes e seguros, novos fármacos ou protótipos para a síntese de substâncias químicas potencialmente ativas. O objetivo da presente revisão é destacar os trabalhos publicados sobre plantas leishmanicidas da Amazônia Brasileira e motivar um maior interesse para pesquisas na área.Leishmaniasis is a serious public health problem, occurring in 98 countries. Brazil is responsible for almost all notified cases of Visceral Leishmaniasis (VL) in the Americas, and the disease is in the process of urbanization. Tegumentary Leishmaniasis (TL) also has a wide distribution worldwide. In Brazil, the Northern region has the highest number of confirmed cases, most of them caused by Leishmania (L) amazonensis. The drugs of first choice for the treatment of leishmaniasis are derived from pentavalent antimony (Sb5 +), such as glucantime, the most widely used in Brazil. Antimonial drugs have several adverse effects; moreover, in recent years, the problem has worsened with the emergence of parasite resistance to these drugs. The need for new effective leishmanicidal drugs has aroused interest in the research of plants used for this purpose in endemic countries, leading to the recognition of active natural products, which may represent chemical-biological markers for the development of effective and safe herbal medicines, new drugs Or prototypes for the synthesis of potentially active chemicals. The objective of the present review is to highlight the published works on leishmanicidae plants of the Brazilian Amazon and motivate a greater interest for researches in the area