180799-27-3Relevant academic research and scientific papers
Synthesis and antiplatelet activity of antithrombotic thiourea compounds: Biological and structure-activity relationship studies
Louren?o, André Luiz,Saito, Max Seidy,Dorneles, Luís Eduardo Gomes,Viana, Gil Mendes,Sathler, Plínio Cunha,De Aguiar, Lúcia Cruz Sequeira,De Pádula, Marcelo,Domingos, Thaisa Francielle Souza,Fraga, Aline Guerra Manssour,Rodrigues, Carlos Rangel,DeSousa, Valeria Pereira,Castro, Helena Carla,Cabral, Lucio Mendes
, p. 7174 - 7200 (2015)
The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N′-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p) displayed IC50 values ranging from 29 to 84 μM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations.
Antileishmanial thioureas: Synthesis, biological activity and in Silico evaluations of new promising derivatives
Viana, Gil Mendes,Do Amaral, Lilian Henriques,Meireles, Paloma Wetler,Nunes, Raquel Pinto,Da Silva, Luiz Cláudio Rodrigues Pereira,De Sousa, Valeria Pereira,Sathler, Plínio Cunha,Cabral, Lucio Mendes,Soares, Deivid Costa,Saraiva, Elvira Maria,Santana, Marcos Vinicius,Castro, Helena Carla,De Sequeira Aguiar, Lúcia Cruz,Rodrigues, Carlos Rangel,Abreu, Paula Alvarez
, p. 911 - 919 (2018/10/31)
Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania. Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N,N′-disubstituted thioureas against Leishmania amazonensis, with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives (3e, 3i, 3k, 3l, 3p, 3q, 3v, 3x and 3z) were active against parasite promastigotes (IC50 21.48–189.10μM), with low cytotoxicity on mice peritoneal macrophages (CC50>200μM), except for thiourea 3e (CC50=49.22μM). After that, the most promising thioureas (3k, 3l, 3p, 3q and 3v) showed IC50 ranging from 70 to 150μM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p, the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.
A concise synthesis of substituted thiourea derivatives in aqueous medium
Maddani, Mahagundappa R.,Prabhu, Kandikere R.
supporting information; experimental part, p. 2327 - 2332 (2010/07/02)
(Figure Presented) An efficient method for the synthesis of symmetrical and unsymmetrical substituted thiourea derivatives by means of simple condensation between available building blocks such as amines and carbon disulfide in aqueous medium is presented. This protocol works smoothly with aliphatic primary amines to afford various di- and trisubstituted thiourea derivatives. The present method is also useful in synthesizing various substituted 2-mercapto imidazole heterocycles. This method proceeds through a xanthate (amino dithiol deivative) intermediate, unlike isothiocyanate as in an earlier known method.
