Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi

Filho, Gevanio Bezerra de Oliveira; Cardoso, Marcos Veríssimo de Oliveira; Espíndola, José Wanderlan Pontes; Silva, Dayane Albuquerque Oliveira e; Ferreira, Rafaela Salgado; Coelho, Pollyanne Lacerda; Anjos, Pâmela Silva dos; Santos, Emanuelle de Souza; Meira, Cássio Santana; Moreira, Diogo Rodrigo Magalhães; Soares, Milena Botelho Pereira; Leite, Ana Cristina Lima

doi:10.1016/j.ejmech.2017.09.047

Cited by 47 publications

(30 citation statements)

References 49 publications

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“…Aromatic carbons provide their signals between 160 and 114 ppm. As a representative example of related structures, the close range of 13 C NMR shifts of CϭS (179) for derivative 22 and CϭSe (183) for selenourea derivative 48 indicates their chemical similarity to CϭO (156) of urea derivative 11. Most of the compounds proved to be unstable under the harsh conditions of MS, and therefore the nominal mass was not observed.…”

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confidence: 99%

“…Finally, we further expanded the scope of the reaction to the synthesis of selenoureas in order to assess the importance of the number of selenium atoms in the leishmanicidal activity. Regarding the modulation in the pendent amino groups, various substituents were introduced to the terminal phenyl ring with the purpose of exploring their influence on activity by regulating the electronic and steric features (22). Moreover, both cyclic and acyclic aliphatic chains have been validated as attractive scaffolds for the development of new leishmanicidal drugs, given the structural analogy with leishmanicidal derivatives containing aminoalkyl chains previously reported in the literature (23,24).…”

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confidence: 99%

“…Thus, this spacer causes a drop in the leishmancidal activity in selenoureas, while in ureas and thioreas it is responsible for a significant increase. With regard to the introduction of alkyl side chains, this modification confers a marked leishmanicidal increase in the three series of compounds (9,10,11,20,21,22,46, 47, and 48), with seven of them being more active than miltefosine. This phenomenon indicates that the activity correlates with an increase in the lipophilicity of the compounds.…”

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confidence: 99%

“…C NMR (100 MHz, DMSO-d 6 , ␦): 14.4 (C 6 ),22.5 (C 5 ),26.5 (C 3 ),30.1 (C 2 ), 31.5 (C 1 ϩ C 4 ), 118.7 (A ϩ A=, C 3 ϩ C 5 ), 121.4 (A ϩ A=, C 1 ), 134.4 (A ϩ A=, C 2 ϩ C 6 ), 141.7 (A ϩ A=, C 4 ), 155.4 (CϭO); MS (m/z % abundance): 172(25), 149 (56), 123 (100), 91 (55), 56 (74); analysis calculated for C26 H 38 N 4 O 2 Se 2 ·1/2 H 2 O (%): C, 51.6; H, 6.2; N, 9.2. Found: C, 51.6; H, 6.0; N, 9.1.…”

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confidence: 99%

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Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides

Díaz

Lucio

Moreno

et al. 2019

Antimicrob Agents Chemother

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A novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Thirteen of the synthesized compounds showed a significant antileishmanial activity, with 50% effective concentration (EC 50 ) values lower than that for the reference drug miltefosine (EC 50 , 2.84 M). In addition, the derivatives 9, 11, 42, and 47, with EC 50 between 1.1 and 1.95 M, also displayed excellent selectivity (selectivity index ranged from 12.4 to 22.7) and were tested against infected macrophages. Compound 11, a derivative with a cyclohexyl chain, exhibited the highest activity against intracellular amastigotes, with EC 50 values similar to those observed for the standard drug edelfosine. Structure-activity relationship analyses revealed that N-aliphatic substitution in urea and selenourea is recommended for the leishmanicidal activity of these analogs. Preliminary studies of the mechanism of action for the hit compounds was carried out by measuring their ability to inhibit trypanothione reductase. Even though the obtained results suggest that this enzyme is not the target for most of these derivatives, their activity comparable to that of the standards and lack of toxicity in THP-1 cells highlight the potential of these compounds to be optimized for leishmaniasis treatment.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides

Díaz

Lucio

Moreno

et al. 2019

Antimicrob Agents Chemother

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“…One of the directions for the design of new antitrypanosomal agents using a molecular hybridization approach is the utilization of hydrazone fragments (Figure 9) as the linker group for the connection of the thiazole/4-thiazolidinone scaffold with the other molecular fragments [117,[141][142][143][144][145][146][147].…”

Section: -Thiazolidinone Frame In the Design Of Antitrypanosomalsmentioning

confidence: 99%

Thiazolidinone-Related Heterocyclic Compounds as Potential Antitrypanosomal Agents

Kryshchyshyn¹,

Kaminskyy²,

Grellier³

et al. 2021

Azoles - Synthesis, Properties, Applications and Perspectives

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Human African trypanosomiasis (HAT) and Chagas disease are neglected tropical diseases (NTDs) due to parasite protists from the Trypanosoma genus transmitted by insect vectors. Trypanosomiases affect mostly poor populations in the developing countries, and the development of new antitrypanosomal drugs is underinvested by governments and the pharmaceutical industry. In this chapter, we described the development of 4-thiazolidinone and thiazole derivatives with heterocyclic fragments which exhibit good inhibition of trypanosome growth and might constitute potential candidates for the development of new drugs against trypanosomiasis. Antitrypanosomal design, mainly within structure-based design, led to the synthesis of 5-ene-4-thiazolidinone-3-alkanecarboxylic acids; 2,3-disubstituted 4-thiazolidinones; thiazolidinone-pyrazoline, phenylindole-thiazolidinone, and imidazothiadiazole-thiazolidinone hybrids; as well as 4-thiazolidinone-based fused heterocycles, especially thiopyrano[2,3-d]thiazoles, and non-thiazolidinone compounds-namely, isothiocoumarine derivatives. Moreover, antitrypanosomal 4-thiazolidinones are of special interest in the search for new antimalarial and antileishmanial agents. Also many active anticancer agents among the abovementioned 4-thiazolidinones have been discovered.

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Mini Review on The Synthesis and Biological Impact of Thiazoles

2023

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This review discusses the most recently reported documents available on the chemistry of thiazoles. In addition, it covers the biological impact of different thiazole based compounds. The information mentioned in this review about the different physico‐chemical characters’ and synthetic paths of such important heterocyclic system take especial attraction and consideration of the biomedicinal chemists to make combinatorial library and exert more efforts in the search of thiazoles.

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Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi

Cited by 47 publications

References 49 publications

Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides

Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides

Thiazolidinone-Related Heterocyclic Compounds as Potential Antitrypanosomal Agents

Mini Review on The Synthesis and Biological Impact of Thiazoles

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