Design, synthesis, and in vitro and in vivo anticancer activity studies of new (S)-Naproxen thiosemicarbazide/1, 2, 4-triazole derivatives. (9th March 2022)

• Record Type: Journal Article
• Authors: Han, M.İhsan; Tunç, Cansu Ümran; Atalay, Pınar; Erdoğan, Ömer; Ünal, Gökhan; Bozkurt, Mehmet; Aydın, Ömer; Çevik, Özge; Küçükgüzel, Ş. Güniz
• Is Part Of: New journal of chemistry. Volume 46:Number 13(2022)
• Page Start: 6046
• Page End: 6059
• Publication Date: 2022-03-09
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d1nj05899a
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : This study includes the synthesis of new Naproxen derivatives and in vitro – in vivo molecular mechanistic studies. Abstract : In this study, a series of novel ( S )-Naproxen derivatives bearing a thiosemicarbazide/1, 2, 4-triazole moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral ( 1 H– 13 C NMR, FT-IR, and HR-MS analyses) methods. All of the synthesized compounds (3a–m, 4a–j ) were screened for anticancer activity against human breast cancer cell line MDA-MB-231. Among them, ( S )-4-(2, 4-dichlorophenyl)-5-[1-(6-methoxynaphthalen-2-yl)ethyl]-4 H -1, 2, 4-triazole-3-thione (4b ) showed the most potent anticancer activity with a good selectivity (IC50 = 9.89 ± 2.4 μM). Inhibition of anti-apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 4b using Western Blotting. Apoptosis was also detected by AO/EB and JC-1 staining. Furthermore, activation of caspase-3 enzyme activity demonstrated apoptosis. The flow cytometric analysis results showed that compound 4b decreases the number of cells in the G2/M phase and increases the cells in the S phase in a dose-dependent manner. The anticancer activity of compound 4b was also investigated. In the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, compound 4b had anticancer activity and reduced the tumor volume at both low (60 mg kg −1 ) and high (120 mg kg −1 ) doses in mice, according to our in vivo results.