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Nitroimidazoles are pharmacophoric groups responsible for important antiparasitic activity against several infectious diseases. 2-Nitroimidazoles are found in some antiparasitic drugs and are one of the main moieties responsible for the biological activities exhibited. As an example, we can mention the drug benznidazole, the only drug available in Brazil for the treatment of Chagas disease. This work describes an efficient methodology for the synthesis of 2-nitro-1-vinyl-1H-imidazole through a simple and direct approach, as well as its full characterization and biological assessment. The antiparasitic evaluation of 2-nitro-1-vinyl-1H-imidazole against Trypanosoma cruzi (Tulahuen C2C4-LacZ strain) showed IC50 = 4.8 μM on amastigotes and low cytotoxicity against LLC-MK2 cells (IC50 > 500 μM), validating 2-nitro-1-vinyl-1H-imidazole as a biologically active structural subunit for anti-T. cruzi activity. The results presented herein demonstrate that 2-nitro-1-vinyl-1H-imidazole can be easily obtained, possessing great potential for use in the design of new antichagasic drugs through a molecular hybridization strategy using known coupling reactions. [ABSTRACT FROM AUTHOR]

The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The variously substituted triazole derivatives were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain), with IC50s = 18.3 and 8.87 μM against epimastigotes and amastigotes, respectively. [ABSTRACT FROM AUTHOR]

Curcumin (1) an important yellow dye isolated from Curcuma longa rhizomes, exhibits a variety of pharmacological effects such as anti-inflammatory, antioxidant and antiviral activity. Ten curcuminoids (2-11) were synthesized by the condensation of 2,4-pentanedione with differently substituted benzaldehydes, using the boron complex approach, which avoided Knoevenagel condensation at C-3 of the diketone. The curcuminoids were assayed in vitro against Leishmania amazonensis promastigotes using pentamidine isethionate (CAS 140-64-7) as the reference drug. Compound (5) 1,7-bis-(2hydroxy-4-methoxyphenyl)-1,6heptadiene-3,5-dione) was the most effective. [ABSTRACT FROM AUTHOR]

In a previous work, the in vitro and in vivo activity of a series of diarylhep-tanoid derivatives against Leishmania amazonensis has been described. Based on the promising results, ten new com-pounds belonging to the same chemical class were synthesized and have been in-vestigated in relation to their leishmanici-dal activity. The compounds were ob-tained through several chemical modi-fications on the basic structure of curcu-min (1,7-bis-(4-hydroxy-3-methoxy-phenyl)- 1,6-heptadiene-3,5-dione) in an attempt to increase its effectiveness and decrease the potential toxic effects. The drugs were assayed in vitro against L. am-azonensis promastigotes and using penta-midine isethionate as reference drug. The results showed that the most effec-tive compound is 1,7- bis- (4-propargyl-3- methoxyphenyl)-1,6-heptadiene-3,5- dione, which is about ten times more effi-cient than the original curcumin. Never-theless, these results did not allow us to make any correlation between the leish-manicidal activity and the chemical struc-ture of the compounds. [ABSTRACT FROM AUTHOR]

We describe herein an evaluation of trypanocidal effects of the natural alkaloid piperine and twelve synthetic derivatives against epimastigote and amastigote forms of the protozoan parasite Trypanosoma cruzi, the causative agent of the incurable human disease, Chagas' disease. The results obtained point to piperine as a suitable template for the development of new drugs with trypanocidal activity.

In a previous work, the in vitro and in vivo activity of a series of diarylheptanoid derivatives against Leishmania amazonensis has been described. Based on the promising results, ten new compounds belonging to the same chemical class were synthesized and have been investigated in relation to their leishmanicidal activity. The compounds were obtained through several chemical modifications on the basic structure of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in an attempt to increase its effectiveness and decrease the potential toxic effects. The drugs were assayed in vitro against L. amazonensis promastigotes and using pentamidine isethionate as reference drug. The results showed that the most effective compound is 1,7-bis-(4-propargyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, which is about ten times more efficient than the original curcumin. Nevertheless, these results did not allow us to make any correlation between the leishmanicidal activity and the chemical structure of the compounds.