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Machado M

N-cinnamoylation of antimalarial classics: quinacrine analogues with decreased toxicity and dual-stage activity

Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy.
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Bis-alkylamineIndolo[3,2-b]quinolines as hemozoin ligands: implications for antimalarialcytostatic and cytocidal activities

To get insight into the relevance of targeting hemozoin (Hz) crystals, two isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k) indolo[3,2-b]quinolines, were evaluated for their in vitro activity against chloroquine (CQ)-resistant and sensitive strains of Plasmodium falciparum.
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Probing the aurone scaffold against Plasmodium falciparum: design, synthesis and antimalarial activity

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold.
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Whole-Cell SYBR Green I Assay for Antimalarial Activity Assessment

Malaria parasite growth assessment assays using nucleic acid dye SYBR GreenI are frequently compromised by high background readings due to haemoglobin and detergents in lysis buffer. Here, we have assessed and further validated an intact-cell SYBR Green I-based fluorescence assay (Cell-MSF) for antimalarial activity assessment even of highly fluorescent compounds.
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N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodium spp. were assessed along with their in vitro cytotoxicities.
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Treatment of plasmodium chabaudi parasites with curcumin in combination with antimalarial drugs: Drug interactions and implications on the ubiquitin/proteasome system

Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp.
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A review of antimalarial plants used in traditional medicine in communities in Portuguese-speaking countries: Brazil, Mozambique, Cape Verde, Guinea-Bissau, São Tomé and Príncipe and Angola.

The isolation of bioactive compounds from medicinal plants, based on traditional use or ethnomedical data, is a highly promising potential approach for identifying new and effective antimalarial drug candidates.
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N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups.
Ler mais

N-Cinnamoylation of Antimalarial Classics: Quinacrine Analogues with Decreased Toxicity and Dual-Stage Activity

Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported.
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Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold.
Ler mais