Amazonian biodiversity: a view of drug development for Leishmaniasis and malaria

Calderon, Leonardo de Azevedo; Zuliani, Juliana Pavan; Silva, Alexandre de Almeida e; Ciancaglini, Pietro; Silva, Luiz Hildebrando Pereira da; Stábeli, Rodrigo G.

doi:10.1590/s0103-50532009000600003

Cited by 32 publications

(23 citation statements)

References 100 publications

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“…The residue purified by column chromatography on silica gel using hexane/ethyl acetate 8:2 as eluent. General procedure for the preparation of triazole derivatives (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) To a solution of terminal acetylenes 25a-d (2 mmol, 1.0 equiv) and azides 27a-d (2 mmol, 1.0 equiv) in dichloromethane (2 mL) and water (2 mL), were added CuSO 4 .5H 2 O pentahydrate (0.128 mmol, 0.064 equiv) and sodium ascorbate (0.352 mmol, 0.176 equiv). The reaction mixture was stirred for 24 h. Then was added a saturated solution of NH 4 Cl (30 mL) and the product was extracted with dichloromethane (3 × 20 mL).…”

Section: General Remarksmentioning

confidence: 99%

“…Natural products, mainly secondary metabolites, are an important source of bioactive compounds, due to their wide chemical diversity. 10,11 However, natural bioactive compounds may possess unsuitable pharmacological characteristics, such as poor oral absorption, high lipophilicity, or cytotoxicity, which limit their use. These various properties can be modulated or improved with the development of synthetic derivatives.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

Cassamale¹,

Costa²,

Carvalho³

et al. 2016

Journal of the Brazilian Chemical Society

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Sixteen 1,4-diaryl-1,2,3-triazole compounds derived from the natural products veraguensin, grandisin and machilin G were synthesized, with yields of 78-92%. Biological activity tests against Leishmania amazonensis promastigotes showed that three of these compounds were the most active, with maximum inhibitory concentration (IC 50 ) values of 1.1, 3.71 and 7.23 µM. One compound was highly active against Leishmania infantum, with an IC 50 value of 5.2 µM, and one derivative showed an IC 50 value of 28.6 µM against Trypanosoma cruzi trypomastigotes. Regarding structureactivity relationship (SAR), hybrid 1,2,3-triazolic compounds containing a methylenedioxy group, showed the best antileishmanial and antitrypanosomal activities.

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Section: General Remarksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

Cassamale¹,

Costa²,

Carvalho³

et al. 2016

Journal of the Brazilian Chemical Society

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“…The poorest populations often living in 107 and malaria [108][109][110][111] to the mix, the diseases kill several million each year, shorten lives and reduce productivity.…”

Section: Current and Future Developmentsmentioning

confidence: 99%

New approaches to the development of anti-protozoan drug candidates: a review of patents

Cunha

Ramalho

Mancini

et al. 2010

J. Braz. Chem. Soc.

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As doenças causadas por protozoários afetam hoje em dia uma grande parcela da população mundial, provocando muitas mortes e exercendo grande influência na qualidade de vida e no desenvolvimento de muitos países. Essas doenças afetam principalmente países pobres e por isso, a pesquisa e o desenvolvimento de novos fármacos são negligenciados. De fato, a maioria das drogas usadas no tratamento dessas doenças data de décadas passadas e apresentam muitas limitações, incluindo o aparecimento da resistência às drogas. Este artigo tem como foco os mais recentes desenvolvimentos publicados no campo de patentes, entre 2001-2008, com especial atenção a promissores compostos atuando contra tripanossomíase, leishmaniose, malária, toxoplasmose, amebíase, giardíase, balantidíase e pneumocistose.Protozoan infections are parasitic diseases that affect hundreds of millions of people worldwide, but have been largely neglected for drug development because they affect poor people in poor regions of the world. Most of the current drugs used to treat these diseases are decades old and have many limitations, including the emergence of drug resistance. This review will focus on the most recent developments, from 2001 to 2008, published in the field of patents and publications, paying particular attention to promising compounds acting against trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, amebiasis, giardiasis, balantidiasis and pneumocystosis, their chemistry and biological evaluation, and to new chemical and pharmaceutical processes.

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“…However, such compounds exhibit poor pharmacokinetic properties and low bioavailability [10,11], which shows the importance of investigating the potentiality of compounds from natural products as a source of new anti-HCV agents [10]. Molecules from natural products are usually distinguished by their greater susceptibility to being absorbed by the human organism in comparison to synthetic substances [13].…”

Section: Introductionmentioning

confidence: 99%

“…This study comprises a virtual screening that employed a database of compounds with 664 molecular structures from natural products extracted from vegetal species of the Amazon region, the area with the richest biodiversity in the world and an important source of therapeutically effective compounds [13]. A consensual analysis from different docking programs was further applied to the results of the virtual screening.…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening and Molecular Dynamics Simulations from a Bank of Molecules of the Amazon Region Against Functional NS3-4A Protease-Helicase Enzyme of Hepatitis C Virus

Pinheiro

Duarte

Alves

et al. 2015

Appl Biochem Biotechnol

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Hepatitis C virus (HCV) infection is a disease that affects approximately 3% of the global population and requires new therapeutic agents without the inconvenience associated with current anti-HCV treatment. This paper reports on a study of a virtual screening and a molecular dynamics simulation of compounds derived from natural products from the Amazon region that are potentially effective against the NS3-4A enzyme of HCV, which plays an important role in the replication process of this virus. According to the results of the molecular docking calculations and subsequent consensual analysis, the best scored compounds showed interactions between hydrogen and residues of the catalytic triad as well as interactions with residues that guide ligands to the active site of the enzyme. They also showed stability in the molecular dynamics simulation, as the structures preserved important interactions at the active site of the enzyme. The root mean square deviation (RMSD) values were stabilized at the end of the simulation time. Such compounds are considered promising as novel therapies against HCV.

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Amazonian biodiversity: a view of drug development for Leishmaniasis and malaria

Cited by 32 publications

References 100 publications

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

New approaches to the development of anti-protozoan drug candidates: a review of patents

Virtual Screening and Molecular Dynamics Simulations from a Bank of Molecules of the Amazon Region Against Functional NS3-4A Protease-Helicase Enzyme of Hepatitis C Virus

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