TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI

Şengül Dilem Doğan; Sümeyye Uğur; Ayşe Kübra Karaboğa Arslan; Ebru Öztürk; Ahmet Cumaoğlu; Mükerrem Betül Yerer

doi:10.34108/eujhs.493005

TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI

Abstract

Tiyenil-tiyazol-aril-tiyoüre türevleri (4a-4e) amino-4-(2-tiyenil)tiyazol ve fenilizotiyasiyanatların reaksiyonları sonucu sentezlenmiştir. Sentezlenen bileşikler IR, ¹H-NMR ve kütle spektrumları ile karekterize edildi. Beş tiyoüre türevinin anti-proliferatif etkileri A549 (KHDAK) hücrelerinde gerçek zamanlı hücre analizörü xCELLigence sistemi ile incelendi. Gerçek zamanlı sistemde sitotoksik olduğu gösterilmiş olan 2 tiyoürenin moleküler etki mekanizmaları, mitokondriyal membran potansiyeli ΔψM spektrofotometrik olarak, sitokrom c western blot methoduyla ve Bcl-2 ise qRT-PCR ile araştırılmıştır. 4e diğerlerinden daha etkili bulunmuştur. 4e IC₅₀ değerleri 24 ve 48 saat için sırasıyla 29,6 µM ve 22,3 µM olarak hesaplanmıştır. Bir triflorometil (-CF₃) grubunu içeren 4e molekülü bir anti-kanserojen madde olarak düşünülebilir ve daha ileri araştırmalar yapılabilir.0000-0003-1761-188X

Keywords

Tiyoüre,Antikanser activite,Tiyazol,Sentez

References

1. Auer H, Oehler R, Lindner R, et al. Characterisation of genotoxic properties of 2′, 2′-difluorodeoxycytidine. Mutat Res Genet Toxicol Environ Mutagen, 1997; 393: 165-173.
2. Aydemir N and Bilaloğlu R. Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo. Mutat Res Genet Toxicol Environ Mutagen, 2003; 537: 43-51.
3. Chen J-N, Wang X-F, Li T, et al. Design, synthesis, and biological evaluation of novel quinazolinyl-diaryl urea derivatives as potential anticancer agents. Eur J Med Chem, 2016; 107: 12-25.
4. Kumbhare RM, Kumar KV, Ramaiah MJ, et al. Synthesis and biological evaluation of novel Mannich bases of 2-arylimidazo [2, 1-b] benzothiazoles as potential anti-cancer agents. Eur J Med Chem, 2011; 46: 4258-4266.
5. Sadeghian-Rizi S, Khodarahmi GA, Sakhteman A, et al. Biological evaluation, docking and molecular dynamic simulation of some novel diaryl urea derivatives bearing quinoxalindione moiety. Res Pharm Sci, 2017; 12: 500.
6. Taleghani A, Nasseri MA, and Iranshahi M. Synthesis of dual-action parthenolide prodrugs as potent anticancer agents. Bioorg Chem, 2017; 71: 128-134.
7. Wang M, Xu S, Lei H, et al. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold. Bioorg Med Chem, 2017; 25: 5754-5763.
8. Decker M. Hybrid molecules incorporating natural products: applications in cancer therapy, neurodegenerative disorders and beyond. Curr Med Chem, 2011; 18: 1464-1475.

9. Al-Showiman SS, Soliman SM, Ghabbour HA, and AlDamen MA. Synthesis, characterization, X-ray structure, computational studies, and bioassay of novel compounds combining thiophene and benzimidazole or 1, 2, 4-triazole moieties. Chem Cent J, 2017; 11: 51.
10. Dos Santos FA, Pereira MC, de Oliveira TB, et al. Anticancer properties of thiophene derivatives in breast cancer MCF-7 cells. Anti-Cancer Drugs, 2018; 29: 157-166.
11. Hafez HN, Alsalamah SA, and El-Gazzar A-R. Synthesis of thiophene and N-substituted thieno [3, 2-d] pyrimidine derivatives as potent antitumor and antibacterial agents. Acta Pharm, 2017; 67: 275-292.
12. Al-Omair MA, Sayed AR, and Youssef MM. Synthesis and Biological Evaluation of Bisthiazoles and Polythiazoles. Molecules, 2018; 23: 1133.
13. Ghorab M and El-Batal A. Synthesis of some new thiazole derivatives. antifungal activity and ultrastructure changes of some mycotoxin producing fungi. Boll Chim Farm, 2002; 141: 110-117.
14. Mohareb RM, Abdallah AE, and Ahmed EA. Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4, 5, 6, 7-tetrahydrobenzo [b] thiophene-3-carbonitrile. Acta Pharm, 2017; 67: 495-510.
15. Begum S, Choudhary MI, and Khan KM. Synthesis, phytotoxic, cytotoxic, acetylcholinesterase and butrylcholinesterase activities of N, N′-diaryl unsymmetrically substituted thioureas. Nat Prod Res, 2009; 23: 1719-1730.
16. Chen L-J, Bao J, Mei F-M, and Li G-X. Oxidative carbonylation of aniline to N, N′-diphenyl urea catalyzed by cobalt (II)–Schiff base complex/pyridine catalytic system. Catal Commun, 2008; 9: 658-663.
17. Jiang N, Bu Y, Wang Y, et al. Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors. Molecules, 2016; 21: 1572.
18. Liu W, Zhou J, Zhang T, et al. Design and synthesis of thiourea derivatives containing a benzo [5, 6] cyclohepta [1, 2-b] pyridine moiety as potential antitumor and anti-inflammatory agents. Bioorg Med Chem Lett, 2012; 22: 2701-2704.
19. Özgeriş B, Akbaba Y, Özdemir Ö, et al. Synthesis and Anticancer Activity of Novel Ureas and Sulfamides Incorporating 1-Aminotetralins. Arch Med Res, 2017; 48: 513-519.
20. Antúnez D-JB, Greenhalgh MD, Fallan C, et al. Enantioselective synthesis of 2, 3-disubstituted trans-2, 3-dihydrobenzofurans using a Brønsted base/thiourea bifunctional catalyst. Org Biomol Chem, 2016; 14: 7268-7274.
21. Chen J, Liu D, Butt N, et al. Palladium‐Catalyzed Asymmetric Hydrogenation of α‐Acyloxy‐1‐arylethanones. Angew Chem Int Ed, 2013; 52: 11632-11636.
22. Zhu Y-P, Yuan J-J, Zhao Q, et al. I 2/CuO-catalyzed tandem cyclization strategy for one-pot synthesis of substituted 2-aminothiozole from easily available aromatic ketones/α, β-unsaturated ketones and thiourea. Tetrahedron, 2012; 68: 173-178.
23. Hassan M, Watari H, AbuAlmaaty A, et al. Apoptosis and molecular targeting therapy in cancer. BioMed Res Int, 2014; 2014.
24. Sinha K, Das J, Pal PB, and Sil PC. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol, 2013; 87: 1157-1180.
25. Czabotar PE, Lessene G, Strasser A, and Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol, 2014; 15: 49.
26. Ly JD, Grubb D, and Lawen A. The mitochondrial membrane potential (Δψm) in apoptosis; an update. Apoptosis, 2003; 8: 115-128.
27. McConkey DJ, Choi W, Marquis L, et al. Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev, 2009; 28: 335-344.
28. Yang J, Liu X, Bhalla K, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science, 1997; 275: 1129-1132.
29. Huang X-C, Wang M, Pan Y-M, et al. Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid. Eur J Med Chem, 2013; 69: 508-520.
30. Lv P-C, Li H-Q, Sun J, et al. Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg Med Chem Lett, 2010; 18: 4606-4614.
31. Madabhushi S, Mallu KKR, Vangipuram VS, et al. Synthesis of novel benzimidazole functionalized chiral thioureas and evaluation of their antibacterial and anticancer activities. Bioorg Med Chem Lett, 2014; 24: 4822-4825.
32. Qiao L, Huang J, Hu W, et al. Synthesis, characterization, and in vitro evaluation and in silico molecular docking of thiourea derivatives incorporating 4-(trifluoromethyl) phenyl moiety. J Mol Struct, 2017; 1139: 149-159.
33. Tokala R, Bale S, Janrao IP, et al. Synthesis of 1, 2, 4-triazole-linked urea/thiourea conjugates as cytotoxic and apoptosis inducing agents. Bioorg Med Chem Lett, 2018; 28: 1919-1924.
34. Xing Y, Zhang W, Song J, et al. Anticancer effects of a novel class rosin-derivatives with different mechanisms. Bioorg Med Chem Lett, 2013; 23: 3868-3872.

Details

Primary Language

Turkish

Subjects

Pharmacology and Pharmaceutical Sciences

Journal Section

Research Article

Authors

Şengül Dilem Doğan ^*
0000-0003-1761-188X
Türkiye

Sümeyye Uğur This is me

Ayşe Kübra Karaboğa Arslan This is me

Ebru Öztürk This is me

Ahmet Cumaoğlu

Mükerrem Betül Yerer

Publication Date

September 20, 2019

Submission Date

December 6, 2018

Acceptance Date

May 13, 2019

Published in Issue

Year 2019 Volume: 28 Number: 2

DOI

https://doi.org/10.34108/eujhs.493005

IZ

https://izlik.org/JA27GE63TR

Cite

RIS / Bibtex

APA

Doğan, Ş. D., Uğur, S., Karaboğa Arslan, A. K., Öztürk, E., Cumaoğlu, A., & Yerer, M. B. (2019). TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI. Sağlık Bilimleri Dergisi, 28(2), 87-93. https://doi.org/10.34108/eujhs.493005

AMA

1.Doğan ŞD, Uğur S, Karaboğa Arslan AK, Öztürk E, Cumaoğlu A, Yerer MB. TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI. Sağlık Bilimleri Dergisi. 2019;28(2):87-93. doi:10.34108/eujhs.493005

Chicago

Doğan, Şengül Dilem, Sümeyye Uğur, Ayşe Kübra Karaboğa Arslan, Ebru Öztürk, Ahmet Cumaoğlu, and Mükerrem Betül Yerer. 2019. “TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI”. Sağlık Bilimleri Dergisi 28 (2): 87-93. https://doi.org/10.34108/eujhs.493005.

EndNote

Doğan ŞD, Uğur S, Karaboğa Arslan AK, Öztürk E, Cumaoğlu A, Yerer MB (September 1, 2019) TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI. Sağlık Bilimleri Dergisi 28 2 87–93.

IEEE

[1]Ş. D. Doğan, S. Uğur, A. K. Karaboğa Arslan, E. Öztürk, A. Cumaoğlu, and M. B. Yerer, “TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI”, Sağlık Bilimleri Dergisi, vol. 28, no. 2, pp. 87–93, Sept. 2019, doi: 10.34108/eujhs.493005.

ISNAD

Doğan, Şengül Dilem - Uğur, Sümeyye - Karaboğa Arslan, Ayşe Kübra - Öztürk, Ebru - Cumaoğlu, Ahmet - Yerer, Mükerrem Betül. “TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI”. Sağlık Bilimleri Dergisi 28/2 (September 1, 2019): 87-93. https://doi.org/10.34108/eujhs.493005.

JAMA

1.Doğan ŞD, Uğur S, Karaboğa Arslan AK, Öztürk E, Cumaoğlu A, Yerer MB. TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI. Sağlık Bilimleri Dergisi. 2019;28:87–93.

MLA

Doğan, Şengül Dilem, et al. “TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI”. Sağlık Bilimleri Dergisi, vol. 28, no. 2, Sept. 2019, pp. 87-93, doi:10.34108/eujhs.493005.

Vancouver

1.Şengül Dilem Doğan, Sümeyye Uğur, Ayşe Kübra Karaboğa Arslan, Ebru Öztürk, Ahmet Cumaoğlu, Mükerrem Betül Yerer. TİYENİL-TİYAZOL-ARİL-TİYOÜRE HİBRİT MOLEKÜLLERİN SENTEZİ VE BİYOLOJİK AKTİVİTELERİNİN APOPTOTİK YOL ÜZERİNDEN ANTİ-KANSER ETKİLERİNİN ARAŞTIRILMASI. Sağlık Bilimleri Dergisi. 2019 Sep. 1;28(2):87-93. doi:10.34108/eujhs.493005

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Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety

New Journal of Chemistry

https://doi.org/10.1039/D1NJ00150G