Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles

Abstract

Synthesis and investigation of antimicrobial activity of 22 novel thiazoles and selenazoles derived from dihydro-2H-thiopyran-4(3H)-one are presented. Additionally, anticonvulsant activity of six derivatives is examinated. Among the derivatives, compounds 4a-f, 4i, 4k, 4 l, 4n, 4o-s and 4v have very strong activity against Candida spp. with MIC ¼ 1.95-15.62 mg/ml. In the case of compounds 4a-f, 4i, 4k, 4 l, 4n, 4o, 4r and 4s, the activity is very strong against some strains of Candida spp. isolated from clinical materials, with MIC ¼ 0.98 to 15.62 mg/ml. Additionally, compounds 4n-v are found to be active against Gram-positive bacteria with MIC ¼ 7.81-62.5 mg/ml. The results of anticonvulsant screening reveal that compounds 4a, 4b, 4m and 4n demonstrate a statistically significant anticonvulsant activity in the pentylenetetrazole model, whereas compounds 4a and 4n showed protection in 6-Hz psychomotor seizure model. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test. We also performed quantum chemical calculation of interaction and binding energies in complex of 4a with cyclodextrin.

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

“…Our earlier studies have shown that incorporation of cyclopentylmethylene and tetrahydro-2 H -thiopyran-4-yl fragments with hydrazinylthiazole moiety was a successful strategy to receive significant anticonvulsant activity in mouse models of seizures (Łączkowski et al 2016d ) and high antifungal activity against clinical isolates of Candida spp. (Łączkowski et al 2016a ).…”

“…Hydrazinylthiazole moiety seems to be a good scaffold to generate a variety of antibacterial (Karegoudar et al 2008 ; Mohammad et al 2015 ; Zhao et al 2017 ; Łączkowski et al 2016a , 2017 ), antifungal (Łączkowski et al 2016b ; Carradori et al 2013 ; Chimenti et al 2007 ), anti- Trypanosoma cruzi (de Oliveira Filho et al 2017 ), and anticancer (Łączkowski et al 2016c ; Łączkowski et al 2014a ) drugs. Our earlier studies have shown that incorporation of cyclopentylmethylene and tetrahydro-2 H -thiopyran-4-yl fragments with hydrazinylthiazole moiety was a successful strategy to receive significant anticonvulsant activity in mouse models of seizures (Łączkowski et al 2016d ) and high antifungal activity against clinical isolates of Candida spp.…”

Synthesis of Various Derivatives of [1,3]Selenazolo[4,5‐d]pyrimidine and Exploitation of These Heterocyclic Systems as Antibacterial, Antifungal, and Anticancer Agents

“…[2] In addition, it plays a pivotal role in the activity of various enzymes such as thioredoxin reductase, iodothyronine deiodinase, selenophosphate synthetase, and selenoprotein P. [3][4][5][6][7] Based on a large variety of chemical, physical, and biological properties associated with the presence of selenium, the synthesis of many Se-containing heterocycles has been developed as a very active research area. [8,9,18,[10][11][12][13][14][15][16][17] A diversity of organic selenium derivatives has earned well-deserved reputation for effective biocidal, [19,20] antifungal, [21][22][23][24] antiinflammatory, [25] anti-HIV, [26][27][28] antioxidant, [23,[29][30][31][32][33][34] free radical scavenging, [29,31,33,[35][36][37][38] antimicrobial, [22,24,39] anticonvulsant, [39] histone deacetylase …”

“…[57][58][59][60][61][62] Amongst heterocyclic organoselenium cores, the 1,3-selenazole skeleton has received much attention in many pharmacologically active substances like selenazofurin (I) and amselamine (II). (Figure 1) Biological properties such as antioxidant, [13] anticancer, [8,63,64] human carbonic anhydrase IX inhibitory, [12] antimicrobial and anticonvulsant [39] activities are the other worldwide high profile of 1,3-selenazoles.…”

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

“…Phenytoin and carbamazepine are the most commonly used standard drugs which act by inhibition of voltage‐gated sodium ion channels (VGSCs). These drugs are also reported to enhance GABA‐mediated response and alleviate seizures .…”