A theoretical view on the stereochemistry of 1,3-benzoxazol-2-(3H)-ylidenes obtained from double vinylic substitution.

2-(1,3-Benzoxazol-2(3H)-ylidene)-3-oxo-3-phenylpropanenitrile (1) and methyl-2-(1,3-benzoxazol-2(3H)-ylidene)(cyano)acetate (2) are observed as single isomers by NMR spectroscopy. A theoretical study was carried out to investigate if this is due to the exclusive presence of the most stable diastereoisomer or if the ene moiety undergoes fast rotation, thereby allowing for the observation of an average conformer. Indeed, the pronounced stabilization of the E stereoisomer, attributed to intramolecular hydrogen bonding, makes it the single obtained product.

Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals.

N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity.

Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents.

Continuous efforts have been made to discover new drugs for the treatment of Chagas' disease, human African trypanosomiasis, and leishmaniasis. We have previously reported the synthesis and antileishmanial and antitrypanosomal (Y strain) properties of 2,3-disubstituted quinoxalines. Considering their promising antiparasitic potential, the present study was conducted to expand our search and take advantage of high-throughput assays to investigate the effects of quinoxaline derivatives against Leishmania donovani, Trypanosoma brucei, and Trypanosoma cruzi (Tulahuen strain).

Benzoxazoles as novel herbicidal agents.

Background: Despite the need to develop new herbicides with different modes of action, due to weed resistance, many important classes of compounds have been studied poorly for this purpose. Benzoxazoles are considered privileged structures because of their biological activities, but their phytotoxic activities have not received a lot of attention until now.

Results: Double vinylic substitution reactions were carried out to furnish four 2-nitromethylbenzoxazoles and one oxazolidine.

A potent larvicidal agent against Aedes aegypti mosquito from cardanol.

Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins.

In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis.

Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against Leishmania amazonensis The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined.

Molecular design, synthesis and evaluation of 2,3-diarylquinoxalines as estrogen receptor ligands.

Selective Estrogen Receptor Modulators (SERMs) are characteristically capable of being antagonist and agonist of estrogen receptors and, therefore, they can inhibit or stimulate estrogen production in different tissues. Aiming to contribute to the identification of new synthetic SERMs candidates, the basic skeletons of raloxifene and tamoxifene were used as model. Here of, a set of 2,3-diaryl-quinoxalines having 2-(piperidin-1- yl)ethanol in the side chain have been synthesized and evaluated against human mammary carcinoma cells estrogen dependent (MCF-7), as well as in recombinant yeast assays (RYA) expressing estrogen receptor.

Synthesis and biological evaluation of novel 2,3-disubstituted quinoxaline derivatives as antileishmanial and antitrypanosomal agents.

Quinoxalines belong to the N-containing heterocyclic compounds that stand out as having promising biological activity due to their privileged scaffold. In this work, we report the synthesis, antileishmanial, and antitrypanosomal properties of 46 new 2,3-disubstituted quinoxaline and 40 previously reported derivatives. Among all of the compounds screened for in vitro activity against epimastigotes and trypomastigotes of Trypanosoma cruzi and promastigotes of Leishmania amazonensis as well as mammalian toxicity on LLCMK2 cells and J774 macrophages, analogues from series 5, 6, 7, 9, 12, and 13 displayed high activity at micromolar IC50 and EC50 concentrations.

A quinoxaline derivative as a potent chemotherapeutic agent, alone or in combination with benznidazole, against Trypanosoma cruzi.

Background: Chagas' disease is a condition caused by the protozoan Trypanosoma cruzi that affects millions of people, mainly in Latin America where it is considered endemic. The chemotherapy for Chagas disease remains a problem; the standard treatment currently relies on a single drug, benznidazole, which unfortunately induces several side effects and it is not successful in the cure of most of the chronic patients. In order to improve the drug armamentarium against Chagas' disease, in the present study we describe the synthesis of the compound 3-chloro-7-methoxy-2-(methylsulfonyl) quinoxaline (quinoxaline 4) and its activity, alone or in combination with benznidazole, against Trypanosoma cruzi in vitro.