Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points: • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical

Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.

Synthesis and investigation of antimicrobial activity of fifteen novel thiazoles containing cyclohexene moiety are presented. Among the derivatives, compounds 3a–3d, 3f, 3n, and 3o showed very strong activity against the reference Candida spp. strains with MIC = 0.015–3.91 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control. Compounds 3d, 3f, 3n, 3o showed the highest activity with very strong effect towards most of yeasts isolated from clinical materials with MIC = 0.015–7.81 µg/ml. The cytotoxicity studies for the most active compounds showed that Candida spp. growth was inhibited at noncytotoxic concentrations for the mammalian L929 fibroblast. In addition, a good correlation was obtained between lipophilicity of compounds determined using reversed phase thin-layer chromatography and their antifungal activity.

We have designed novel tropinone-thiazole derivatives that showed high antiproliferative activity against a variety of cancer cell lines via caspase 3/7 activation mechanism. Among the derivatives, compounds 3b-3h were found to exhibit high activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast carcinoma (MCF-7), and skin melanoma (B16-F10) cancer cell lines, with IC50 values of 5.43-11.06 μM. The lead compound 3g increases caspase 3/7 activity in A549 cells 25 times more than the control, and 2 times more than reference drug camptothecin. We have also found that tropinone-thiazole derivatives exhibit high tyrosinase inhibitory activity. The lead compounds 3g and 3h showed tyrosinase inhibition effect, with IC50 values 3.22 and 3.51 μM, respectively. These inhibitory activities are 22 times higher than the activity of kojic acid (IC50 72.27 μM) and 120 times higher than activity of ascorbic acid (IC50 386.5 μM). For compounds 3g and 3h, the experimentally determined lipophilicity correlates very well with their enzymatic activities. These data suggest that presented compounds could constitute lead anticancer drug candidates.

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.