67 documents found, page 1 of 7
High efficacy of chloroquine-derived bile salts in Pluronic F127 micelles again...
Silva, Ana Teresa; Prudêncio, Miguel; Oliveira, Isabel S.; Nogueira, Fátima; Morais, Inês; Santana, Sofia; Ferraz, Ricardo; Workneh, Eyob A.Colloidal nanocarriers can play a key role in the efficacious delivery of drugs, including antimalarials. Here, we investigated the ability of polymeric micelles of the block copolymer F127 to act as nanovehicles for two organic salts derived from chloroquine and human bile acids, namely, chloroquinium cholate (iCQP1) and chloroquinium glycocholate (iCQP1g). We have previously reported the strong in vitro antip...
Surface-active ionic liquids derived from antimalarial drugs and natural lipids...
Ferraz, Ricardo; Silva, Ana Teresa; Oliveira, Isabel S.; Duarte, Denise; Moita, Diana; Nogueira, Fátima; Prudêncio, Miguel; Gomes, PaulaThe use of Ionic Liquids (ILs) in Medicinal and Pharmaceutical Chemistry has been greatly evolving since they were first used as alternative solvents for the chemical synthesis of active pharmaceutical ingredients (APIs). ILs are now used with other purposes in this area, such as adjuvants in drug formulation and delivery, or even as bioactive compounds per se. New ionic structures with biologically relevant pr...
Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative ef...
Fonte, Mélanie; Rôla, Catarina; Santana, Sofia; Ferraz, Ricardo; Prudêncio, Miguel; Almeida, Joana; Ferraz, Ricardo; Prudêncio, CristinaDrug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compound...
Unexpected rearrangement of ivermectin in the synthesis of new derivatives with...
Sulik, Michał; Fontinha, Diana; Steverding, Dietmar; Sobczak, Szymon; Antoszczak, Michał; Prudêncio, Miguel; Huczyński, AdamIvermectin is a sixteen-membered macrolactone "wonder drug" of Nobel prize-honored distinction that exhibits a wide range of antiparasitic activities. It has been used for almost four decades in the treatment of various parasitic diseases in humans and animals. In this paper, we describe the synthesis of the first-in-class ivermectin derivatives obtained via derivatization of the C13 position, along with the un...
Whole-sporozoite malaria vaccines: where we are, where we are going
Moita, Diana; Prudêncio, MiguelThe malaria vaccination landscape has seen significant advancements with the recent endorsement of RTS,S/AS01 and R21/Matrix-M vaccines, which target the pre-erythrocytic stages of Plasmodium falciparum (Pf) infection. However, several challenges remain to be addressed, including the incomplete protection afforded by these vaccines, their dependence on a single Pf antigen, and the fact that they were not design...
A novel 4-aminoquinoline chemotype with multistage antimalarial activity and la...
Ferreira, Letícia Tiburcio; Cassiano, Gustavo Capatti; Alvarez, Luis Carlos Salazar; Okombo, John; Calit, Juliana; Fontinha, Diana; Gil-Iturbe, EvaArtemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs. In this study, we...
SARS-CoV-2 decreases malaria severity in co-infected rodent models
Fraga, Ana; Mósca, Andreia F.; Moita, Diana; Simas, J. Pedro; Nunes-Cabaço, Helena; Prudêncio, MiguelCoronavirus disease 2019 (COVID-19) and malaria, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium parasites, respectively, share geographical distribution in regions where the latter disease is endemic, leading to the emergence of co-infections between the two pathogens. Thus far, epidemiologic studies and case reports have yielded insufficient data on the reciprocal impact ...
Combining natural bile acids with old basic drugs affords new triple stage anti...
Silva, Ana Teresa; Oliveira, Isabel; Duarte, Denise; Moita, Diana; Prudêncio, Miguel; Nogueira, Fátima; Ferraz, Ricardo; Marques, Eduardo F.Ionic liquids (ILs) are special organic salts that have been gaining momentum in medicinal chemistry. Despite their simple and cost-effective synthesis, ILs offer an easy access to structures of biological interest by combining bioactive molecules with opposite polarities, e.g., via simple ionic pairing of an acid with a base. This makes ILs of special interest for treating malaria. Since this disease is preval...
Design, synthesis and antiplasmodial evaluation of new amide-, carbamate-, and ...
Marinović, Marina; Rimac, Hrvoje; de Carvalho, Lais Pessanha; Rôla, Catarina; Santana, Sofia; Pavić, Kristina; Held, Jana; Prudêncio, MiguelMalaria, one of the oldest parasitic diseases, remains a global health threat, and the increasing resistance of the malaria parasite to current antimalarials is forcing the discovery of new, effective drugs. Harmicines, hybrid compounds in which harmine/β-carboline alkaloids and cinnamic acid derivatives are linked via an amide bond or a triazole ring, represent new antiplasmodial agents. In this work, we used ...
Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 C...
da Silva, Gustavo; Luz, André F. S.; Duarte, Denise; Fontinha, Diana; Silva, Vera L. M.; Almeida Paz, Filipe A.; Madureira, Ana M.; Simões, SandraA multistep and diversity-oriented synthetic route aiming at the A3 coupling/domino cyclization of o-ethynyl anilines, aldehydes and s-amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross-coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwen...