Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids

Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines

Effect of the antimicrobial peptide gomesin against different life stages of Plasmodium spp.

While seeking strategies for interfering with Plasmodium development in vertebrate/invertebrate hosts, we tested the activity of gomesin, an antimicrobial peptide isolated from the hemocytes of the spider Acanthoscurria gomesiana. Gomesin was tested against asexual, sexual and pre-sporogonic forms of Plasmodium falciparum and Plasmodium berghei parasites. the peptide inhibited the in vitro growth of intraerythrocytic forms of P. falciparum. When gomesin was added to in vitro, culture of P. berghei mature gametocytes, it significantly inhibited the exflagellation of male gametes and the formation of ookinetes. in vivo, the peptide reduced the number of oocysts of both Plasmodium species in Anopheles stephensi mosquitoes, and did not appear to affect the mosquitoes. These properties make gomesin an excellent candidate as a transmission blocking agent for the genetic engineering of mosquitoes. (c) 2007 Elsevier Inc. All rights reserved.Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Malaria, BR-30190002 Belo Horizonte, MG, BrazilJohns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Scienc

Design and Synthesis of New Chacones Substituted with Azide/Triazole Groups and Analysis of Their Cytotoxicity Towards HeLa Cells

A series of new chalcones substituted with azide/triazole groups were designed and synthesized, and their cytotoxic activity was evaluated in vitro against the HeLa cell line. O-Alkylation, Claisen-Schmidt condensation and Cu(I)-catalyzed cycloaddition of azides with terminal alkynes were applied in key steps. Fifteen compounds were tested against HeLa cells. Compound 8c was the most active molecule, with an IC50 value of 13.03 µM, similar to the value of cisplatin (7.37 µM)

Design and Synthesis of New Chacones Substituted with Azide/Triazole Groups and Analysis of Their Cytotoxicity Towards HeLa Cells

A series of new chalcones substituted with azide/triazole groups were designed and synthesized, and their cytotoxic activity was evaluated <em>in vitro</em> against the HeLa cell line. <em>O</em>-Alkylation, Claisen-Schmidt condensation and Cu(I)-catalyzed cycloaddition of azides with terminal alkynes were applied in key steps. Fifteen compounds were tested against HeLa cells. Compound <strong>8c</strong> was the most active molecule, with an IC<sub>50</sub> value of 13.03 µM, similar to the value of cisplatin (7.37 µM)

Larvicidal activity of vegetable oils and esterified compounds against Culex quinquefasciatus (Diptera: Culicidae)

Control of Culex quinquefasciatus using chemical insecticides may result in the selection of resistant mosquito strains. Thus, the use of plant-derived products has been studied as alternative for the mosquito control. Fatty acid methyl esters (FAMEs) obtained by transesterification of vegetable oils may result in compounds with larvicidal potential against C. quinquefasciatus. However, little is known about the morphological, physiological or biochemical effects that these FAMEs may have on mosquito larvae. The present study reports the effects of these FAMEs in mosquito larvae. The FAMEs were obtained by transesterification of canola, corn, sunflower, and soybean oils with acid catalysis and the determination of FAMEs composition was done by gas chromatography-mass spectrometry (GC-MS). Larvae of C. quinquefasciatus were exposed to different concentrations of the vegetable oils and FAMEs. Thereby, different FAMEs showed LC50 values ranging from 42.32 to 196.27 mg/L against C. quinquefasciatus larvae. The methyl ester obtained from sunflower oil showed the lowest LC50. Histology of C. quinquefasciatus larvae exposed to LC50 of FAMEs was performed and changes in the midgut and fat body morphology were identified. Therefore, larval mortality and changes in the internal organs suggested that FAMEs might be a promising new class of larvicidalcompounds. Cytotoxicity of FAMEs compounds was assessed with the HeLa human cell line and no effect was observed