RESUMO
Thiazolidine scaffolds have been investigated for decades, due to their wide range of biological activity. In this way, the main objective of this systematic review was to elucidate the anti-inflammatory activity of thiazolidine derivatives against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. From 9718 identified registers, 13 articles were included, where 11 studies evaluated thiazolidinediones. The summary of relevance demonstrated that seven studies (53.8%) were relevant without restrictions, and 6 (46.2%) were relevant with restrictions. The certainty in cumulative evidence was considered moderate and the six studies included in the meta-analysis demonstrated the positive activity of thiazolidinediones against NO production when compared to the negative LPS control.
RESUMO
An organocatalytic [3+2] cycloaddition reaction between thiazolidine-containing ß-ketoester 1 and aryl azides 2 was employed to synthesize new 1,2,3-triazolyl-thiazolidine hybrids 3. In this metal-free approach, twelve compounds were isolated in yields ranging from 23 % to 96 % by using diethylamine (10â mol%) and DMSO at 75 °C for 24â hours. DNA-binding assays were conducted through absorption, emission spectroscopy and viscosimetry analysis, to evaluate the interaction capacity of the studied derivatives with nucleic acids. All the synthesized compounds were evaluated for their interactions with a specific group of compounds containing the pharmacophoric groups triazole and thiazolidine through a molecular docking speculative study, aimed at identifying the interaction profile of these compounds with DNA. The obtained results suggest that 1,2,3-triazolyl-thiazolidine hybrids could be a promising approach in the development of novel therapeutic agents targeting DNA-related processes.
Assuntos
Estrutura Molecular , Tiazolidinas/química , Simulação de Acoplamento Molecular , Reação de Cicloadição , Relação Estrutura-AtividadeRESUMO
Neglected diseases, such as Leishmaniasis, constitute a group of communicable diseases that occur mainly in tropical countries. Considered a public health problem with limited treatment. Therefore, there is a need for new therapies. In this sense, our proposal was to evaluate in vitro two series of thiazolidine compounds (7a-7e and 8a-8e) against Leishmania infantum. We performed in vitro evaluations through macrophage cytotoxicity assays (J774) and nitric oxide production, activity against promastigotes and amastigotes, as well as ultrastructural analyzes in promastigotes. In the evaluation of cytotoxicity, the thiazolidine compounds presented CC50 values between 8.52 and 126.83 µM. Regarding the evaluation against the promastigote forms, the IC50 values ranged between 0.42 and 142.43 µM. Compound 7a was the most promising, as it had the lowest IC50. The parasites treated with compound 7a showed several changes, such as cell body shrinkage, shortening and loss of the flagellum, intense mitochondrial edema and cytoplasmic vacuolization, leading the parasite to cell inviability. In assays against the amastigote forms, the compound showed a low IC50 (0.65 µM). These results indicate that compound 7a was efficient for both evolutionary forms of the parasite. In silico studies suggest that the compound has good oral bioavailability. These results show that compound 7a is a potential drug candidate for the treatment of Leishmaniasis.