Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study

Abstract

Synthesis and investigation of antifungal, anticonvulsant and anti-Toxoplasma gondii activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole 3a–3j are presented. Among the derivatives, compounds 3a–3d and 3f–3j possess very high activity against Candida spp. ATCC with MIC = 0.015–7.81 µg/ml. Compounds 3a–3d and 3f–3j possess also very high activity towards most of strains of Candida spp. isolated from clinical materials with MIC = 0.015–7.81 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control. Additionally, compounds 3c and 3e showed interesting anticonvulsant activities in the MES test, whereas compounds 3f and 3i demonstrated the anticonvulsant activity in PTZ-induced seizures. Noteworthy, none of these compounds impaired animals’ motor skills in the rotarod test. Moreover, thiazoles 3a, 3h, and 3j showed significant anti-Toxoplasma gondii activity, with IC50 values 31–52 times lower than those observed for sulfadiazine. The results of the cytotoxicity evaluation, anti-Candida spp. and anti-Toxoplasma gondii activity studies showed that Candida spp. and Toxoplasma gondii growth was inhibited at non-cytotoxic concentrations for the mouse L929 fibroblast and the African green monkey kidney (VERO) cells. Molecular docking studies indicated secreted aspartic proteinase (SAP) as possible antifungal target.

Review of the synthesis and biological activity of thiazoles

“…Then, the reaction of 2-(Cyclopropylmethylidene)-hydrazinecarboxamide 86 with p-substituted bromoacetophenones yield the thiazole compounds 88 (Scheme 25). [48] In addition, thiazoline derivatives 92 were obtained from the reaction of thioacetamide 89 with dimethyl acetylenedicarboxylate 90 (Scheme 26). The final product was invistigated according to the literature survey [49][50][51][52] and the spectral data…”

Synthesis, antimicrobial activity, and determination of the lipophilicity of ((cyclohex-3-enylmethylene)hydrazinyl)thiazole derivatives

“…The last years of the research have confirmed that thiazole scaffold has diverse biological properties that can be used to treat many diseases, such as microbial infections (Bikobo et al 2017;Secci et al 2012;Łączkowski et al 2018a, 2018bZaki et al 2018;Ansari et al 2018), Parkinson's disease (Carradori et al 2018), cancer (de Santana et al 2018;Łączkowski et al 2014, 2016a, 2016bPiechowska et al 2019;Gomha et al 2018), epilepsy (Siddiqui and Ahsan 2010;Ahangar et al 2011;Łączkowski et al 2016a, 2016b, toxoplasmosis (Schultz et al 2014;Łączkowski et al 2018a, 2018b, and antioxidants (Geronikaki et al 2013;Djukic et al 2018). Considering the above-mentioned findings, we decided to design and synthesize the structure of hybrids incorporating both the thiazole ring and the cyclohexenyl moiety.…”

Efficient Synthesis, Antibacterial, Antifungal, Antioxidant and Cytotoxicity Study of 2‐(2‐Hydrazineyl)thiazole Derivatives

“…It has been revealed that compounds containing thiazole skeleton exhibit significant biological activities, which have pulled in consideration of researchers in both medicinal chemistry and chemical biology. In the domain of science, the thiazole skeleton is a key pharmacophore because of its ubiquity in a variety of biological properties . Few noteworthy examples of thiazole derivatives are depicted in Figure .…”