SYNTHESIS, EVALUATION OF ANTIFUNGAL ACTIVITY AND DRUG-LIKENESS OF BENZOYL THIOUREA DERIVATIVES

Yıl 2025, Cilt: 24 Sayı: 47, 217 - 228, 30.06.2025

Şule Erol Günal , Engin Kaplan

https://doi.org/10.55071/ticaretfbd.1588118

Öz

Herein, we report the synthesis of a series of 2-bromobenzoyl-substituted thiourea derivatives. The structures of the synthesized thioureas were characterized by spectroscopic methods. These derivatives, together with 2-fluorobenzoyl thioureas synthesized previously, have been evaluated for their potential antifungal activity. Compounds 2d and 2f showed antifungal activity against Candida albicans. Compound 2f also demonstrated activity against C. parapsilosis. Drug-likeness properties of the compounds were also estimated, and it was found that all compounds showed good drug-likeness properties.

Anahtar Kelimeler

Benzoyl thioureas , antifungal activity , drug-likeness properties , in silico SwissADME

BENZOİL TİYOÜRE TÜREVLERİNİN SENTEZİ, ANTİFUNGAL AKTİVİTESİNİN VE İLAÇ OLABİLİRLİĞİNİN DEĞERLENDİRİLMESİ

Öz

Bu çalışmada, bir dizi 2-bromobenzoil tiyoüre türevleri sentezlenmiştir. Sentezlenen tiyoürelerin yapıları spektroskopik yöntemlerle tanımlanmıştır. Bu türevler, daha önce sentezlenen 2-florobenzoil tiyoürelerle birlikte, potansiyel antifungal aktiviteleri açısından değerlendirilmiştir. Bileşik 2d ve 2f, Candida albicans'a karşı antifungal aktivite göstermiştir. Bileşik 2f ayrıca C. parapsilosis'e karşı aktivite göstermiştir. Bileşiklerin ilaç olabilirlik özellikleri de tahmin edilmiş ve tüm bileşiklerin iyi ilaç olabilirlik özellikleri gösterdiği bulunmuştur.

Anahtar Kelimeler

Benzoil tiyoüreler , antifungal aktivite , ilaç olabilirlik özellikleri , in siliko SwissADME

Kaynakça

• Agili, F.A. (2024). Biological Applications of Thiourea Derivatives: Detailed Review. Chemistry. 6(3), 435-468. https://doi.org/10.3390/chemistry6030025
• Anna, B., Agnieszka, G., Ewa, A., Jolanta, O., Dagmara, K., Marta, S. (2023). In vitro antimycobacterial activity and interaction profiles of diaryl thiourea-copper (II) complexes with antitubercular drugs against Mycobacterium tuberculosis isolates. Tuberculosis. 143, 102412. https://doi.org/10.1016/j.tube.2023.102412
• Calixto S.D., Simão T.L.B.V., Palmeira-Mello M.V., Viana G.M., Assumpção P.W.M.C., Rezende M.G., Santo C.C.E., Mussi V.O., Rodrigues C.R., Lasunskaia E., Souza A. M. T., Cabral L.M., Muzitano M.F. (2022). Antimycobacterial and anti-inflammatory activities of thiourea derivatives focusing on treatment approaches for severe pulmonary tuberculosis. Bioorg. Med. Chem. 53, 116506. https://doi.org/10.1016/j.bmc.2021.116506
• Canudo-Barreras, G., Ortego, L., Izaga, A., Marzo, I., Herrera, R. P., & Gimeno, M. C. (2021). Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties. Molecules, 26(22), 6891. https://doi.org/10.3390/molecules26226891
• Clinical and Laboratory Standards Institute (CLSI). 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, 3rd ed; CLSI document M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA.
• Daina A, Michielin O, Zoete V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 7, 42717. https://doi.org/10.1038/srep42717
• Daina A., Zoete V. (2016). A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules, ChemMedChem, 11, 1117–1121. https://doi.org/10.1002/cmdc.201600182
• Dey S., Patel A., Haloi N., Srimayee S., Paul S., Barik G.K., Akhtar N., Shaw D., Hazarika G., Prusty B.M., Kumar, Santra M.K., Tajkhorshid E., Bhattacharjee S., Manna D. (2023). Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity. J. Med. Chem. 66 (16), 11078-11093 https://doi.org/10.1021/acs.jmedchem.3c00368
• Erol Günal, Ş. (2023). Synthesis Of 2-Fluorobenzoyl Thiourea Derivatives. İstanbul Ticaret Üniversitesi Fen Bilimleri Dergisi, 22(44), 417-424. https://doi.org/10.55071/ticaretfbd.1364818
• Hroch L., Guest P., Benek O., Soukup O., Janockova J., Dolezal R., Kuca K., Aitken L., Smith T.K., Gunn-Moore F., Zala D., Ramsay R.R., Musilek K. (2017). Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment. Bioorg. Med. Chem. 25(3), 1143-1152. https://doi.org/10.1016/j.bmc.2016.12.029
• Potts R.O., Guy R.H. (1992). Predicting skin permeability, Pharm. Res. 9, 663–669 https://doi.org/10.1023/a:1015810312465
• Riccardo, R., Giada, M., Andrea, C., Antimo, G., Emidio, C. (2021). Recent advances in urea- and thiourea-containing compounds: Focus on innovative approaches in medicinal chemistry and organic synthesis. RSC Med. Chem. 12(7), 1046–1064. https://doi.org/10.1039/D1MD00058F
• Seo, H., Kohlbrand, A.J., Stokes, R.W., Chung, J., Cohen, S.M. (2023). Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs. Chem. Commun. 59(16), 2283– 2286. https://doi.org/10.1039/D2CC06596G
• Shivakumara, K.N., Sridhar, B.T. (2021). Review on role of urea and thiourea derivatives of some heterocyclic Scaffold in drug design and medicinal chemistry. Int. J. Chem. Res. Dev. 3(1), 20–25. https://doi.org/10.33545/26646552.2021.v3.i1a.23
• Shulgau Z., Palamarchuk I., Sergazy S., Urazbayeva A., Gulyayev A., Ramankulov Y., Kulakov. I. (2024). Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of Thiourea Derivatives Based on 3-Aminopyridin-2(1H)-Ones. Molecules. 29(15), 3627. https://doi.org/10.3390/molecules29153627
• Strzyga-Łach, P., Chrzanowska, A., Podsadni, K., Bielenica, A. (2021). Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives. Pharmaceuticals, 14, 1097. https://doi.org/10.3390/ph14111097
• Yaqeen, M.A. Rafid, H.A. (2023). Synthesis, Anti-breast Cancer Activity, and Molecular Docking Studies of Thiourea Benzamide Derivatives and Their Complexes with Copper Ion. Trop. J. Nat. Prod. Res. 7(6), 3158–3167. http://www.doi.org/10.26538/tjnpr/v7i6.15