Synthesis and Characterization of New Series Benzothiazole-Dithiocarbamate Derivatives As Potential Antifungal Agents

Öz

Invasive fungal infections (IFIs) have been and will continue to be a great threat to human. Nowadays the aim of many medical research is to discover new safer and more effective antifungal agents. Benzothiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities. Furthermore, dithiocarbamate compounds have become important for many activities due to their chemical structure. In this study, it was aimed to determine being antifungal agents capacity of newly synthesized benzothiazole compounds including dithiocarbamate moiety. The structures of the obtained compounds were elucidated using by 1H-NMR, 13C-NMR and mass spectroscopy.

Anahtar Kelimeler

• Benzothiazole
• Dithiocarbamate
• NMR
• Antifungal activity

Potansiyel Antifungal Ajanlar Olarak Yeni Benzotiyazol-Ditiyokarbamat Türevlerinin Sentezi ve Karakterizasyonu

Öz

İnvaziv mantar enfeksiyonları (IFI'lar) insan için büyük bir tehdit olmuştur ve olmaya devam edecektir. Günümüzde birçok tıbbi araştırmanın amacı yeni daha güvenli ve daha etkili antifungal ajanlar bulmaktır. Benzotiyazol bileşikleri, çok çeşitli biyolojik aktiviteleri nedeniyle farmasötik kimyada önemli bir farmakofor yapıdır. Ayrıca, ditiyokarbamat bileşikleri kimyasal yapıları nedeniyle birçok aktivite için önemli hale gelmiştir. Bu çalışmada, yeni sentezlenen benzotiyazol-ditiyokarbamat bileşiklerinin antifungal etkinliklerinin belirlenmesi amaçlanmıştır. Elde edilen bileşiklerin yapıları, 1H-NMR, 13C-NMR ve kütle spektroskopisi kullanılarak aydınlatılmıştır.

Anahtar Kelimeler

• Benzotiyazol
• Ditiyokarbamat
• NMR
• Antifungal aktivite

Kaynakça

1. Lino, C. I., de Souza, I. G., Borelli, B. M., Matos, T. T. S., Teixeira, I. N. S., Ramos, J. P., ... & de Oliveira, R. B. 2018. Synthesis, molecular modeling studies and evaluation of antifungal activity of a novel series of thiazole derivatives: European Journal of Medicinal Chemistry, vol. 151, pp. 248-260. DOI: 10.1016/j.ejmech.2018.03.083
2. Łukowska-Chojnacka, E., Kowalkowska, A., Gizińska, M., Koronkiewicz, M., Staniszewska, M. 2019. Synthesis of tetrazole derivatives bearing pyrrolidine scaffold and evaluation of their antifungal activity against Candida albicans: European journal of medicinal chemistry, vol. 164, pp, 106-120. DOI: 10.1016/j.ejmech.2018.12.044
3. Zhao, L., Tian, L., Sun, N., Sun, Y., Chen, Y., Wang, X., Zhao, S., Su, X., Zhao, D., Cheng, M. 2019. Design, synthesis, and structure-activity relationship studies of l-amino alcohol derivatives as broad-spectrum antifungal agents: European journal of medicinal chemistry, vol. 177, pp. 374-385. DOI: 10.1016/j.ejmech.2019.05.047
4. Li, B., Wang, K., Zhang, R., Li, B., Shen, Y., Ji, Q. 2019. Design, synthesis and biological evaluation of novel diazaspiro [4.5] decan-1-one derivatives as potential chitin synthase inhibitors and antifungal agents: European journal of medicinal chemistry, vol. 182, pp. 111669. DOI: 10.1016/j.ejmech.2019.111669
5. El Shehry, M. F., Ghorab, M. M., Abbas, S. Y., Fayed, E. A., Shedid, S. A., Ammar, Y. A. 2018. Quinoline derivatives bearing pyrazole moiety: Synthesis and biological evaluation as possible antibacterial and antifungal agents: European journal of medicinal chemistry, vol. 143, pp. 1463-1473. DOI: doi.org/10.1016/j.ejmech.2017.10.046
6. Chandrika, N. T., Dennis, E. K., Shrestha, S. K., Ngo, H. X., Green, K. D., Kwiatkowski, S., ... & Garneau-Tsodikova, S. 2019. N, N′-diaryl-bishydrazones in a biphenyl platform: Broad spectrum antifungal agents: European journal of medicinal chemistry, vol. 164, pp. 273-281. DOI: 10.1016/j.ejmech.2018.12.042
7. Wang, L. L., Battini, N., Bheemanaboina, R. R. Y., Zhang, S. L., Zhou, C. H. 2019. Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation: European journal of medicinal chemistry, vol. 167, pp. 105-123. DOI: 10.1016/j.ejmech.2019.01.072
8. Nalawade, J., Shinde, A., Chavan, A., Patil, S., Suryavanshi, M., Modak, M., ... & Mhaske, P. C. 2019. Synthesis of new thiazolyl-pyrazolyl-1, 2, 3-triazole derivatives as potential antimicrobial agents: European Journal of Medicinal Chemistry, vol. 179, pp. 649-659. DOI: 10.1016/j.ejmech.2019.06.074

9. Sari, S., Kart, D., Öztürk, N., Kaynak, F. B., Gencel, M., Taşkor, G., ... & Dalkara, S. 2019. Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening: European journal of medicinal chemistry, vol. 179, pp. 634-648. DOI: 10.1016/j.ejmech.2019.06.083
10. Elias, R., Benhamou, R. I., Jaber, Q. Z., Dorot, O., Zada, S. L., Oved, K., ... & Fridman, M. 2019. Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles: European journal of medicinal chemistry, vol. 179, pp. 779-790. DOI: 10.1016/j.ejmech.2019.07.003
11. Ji, Q., Deng, Q., Li, B., Li, B., & Shen, Y. 2019. Design, synthesis and biological evaluation of novel 5-(piperazin-1-yl) quinolin-2 (1H)-one derivatives as potential chitin synthase inhibitors and antifungal agents: European journal of medicinal chemistry, vol. 180, pp. 204-212. DOI: 10.1016/j.ejmech.2019.07.035
12. Zhao, S., Zhao, L., Zhang, X., Liu, C., Hao, C., Xie, H., ... & Cheng, M. 2016. Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents: European journal of medicinal chemistry, vol. 123, pp. 514-522. DOI: 10.1016/j.ejmech.2016.07.067
13. Catalano, A., Carocci, A., Defrenza, I., Muraglia, M., Carrieri, A., Van Bambeke, F., ... & Franchini, C. 2013. 2-Aminobenzothiazole derivatives: search for new antifungal agents: European journal of medicinal chemistry, vol. 64, pp. 357-364. DOI: 10.1016/j.ejmech.2013.03.064
14. Singh, M. K., Tilak, R., Nath, G., Awasthi, S. K., Agarwal, A. 2013. Design, synthesis and antimicrobial activity of novel benzothiazole analogs: European journal of medicinal chemistry, vol. 63, pp. 635-644. DOI: 10.1016/j.ejmech.2013.02.027
15. Payaz, D. Ü., Küçükbay, F. Z., Küçükbay, H., Angeli, A., Supuran, C. T. 2019. Synthesis carbonic anhydrase enzyme inhibition and antioxidant activity of novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine moieties: Journal of enzyme inhibition and medicinal chemistry, vol. 34(1), pp. 343-349. DOI: 10.1080/14756366.2018.1553040.
16. Durmaz, R., Köroğlu, M., Küçükbay, H. A. S. A. N., Temel, I., Ozer, M. K., Refiq, M., Cetinkaya, E., Cetinkaya, B., Yoloğlu, S. 1998. Investigation of serum minimal inhibitory concentrations of some benzimidazole, imidazole and benzothiazole derivatives and their effects on liver and renal functions. Arzneimittel-forschung, vol. 48(12), pp. 1179-1184.
17. Küçükbay, H. , Durmaz, B. 1997. Antifungal activity of organic and organometallic derivatives of benzimidazole and benzothiazole. Arzneimittel-forschung, vol. 47(5), pp. 667-670.
18. Mangasuli, S. N., Hosamani, K. M., Managutti, P. B. 2019. Synthesis of novel coumarin derivatives bearing dithiocarbamate moiety: An approach to microwave, molecular docking, Hirshfeld surface analysis, DFT studies and potent anti-microbial agents: Journal of Molecular Structure, vol. 1195, pp. 58-72. DOI: 10.1016/j.molstruc.2018.12.049
19. Rodriguez-Tudela, J.L., Barchiesi, F. 2008. Subcommittee on Antifungal Susceptibility Testing (AFST). EUCAST Definitive Document EDef 7.1: Method for the determination of broth dilution MICs of antifungal agents for fermentative yeast: Clinical Microbiology and Infection, vol. 14(4), pp. 398-405. DOI: /10.1111/j.1469-0691.2007.01935.x
20. Karaburun, A., Acar Çevik, U., Osmaniye, D., Sağlık, B., Kaya Çavuşoğlu, B., Levent, S., Ozkay, Y., Koparal, A.S., Behcet, M., Kaplancıklı, Z. 2018. Synthesis and Evaluation of New 1, 3, 4-Thiadiazole Derivatives as Potent Antifungal Agents, Molecules, vol. 23(12), pp. 3129. DOI: 10.3390/molecules23123129
21. Osmaniye, D., Kaya Cavusoglu, B., Saglik, B. N., Levent, S., Acar Cevik, U., Atli, O., Ozkay, Y., Kaplancikli, Z. A. 2018. Synthesis and anticandidal activity of new imidazole-chalcones: Molecules, 23(4), 831. DOI: 10.3390/molecules23040831