Synthesis and Apoptotic Activities of New 2(3H)-benzoxazolone Derivatives in Breast Cancer Cells

Abstract

Background: 2(3H)-Benzoxazolone derivatives are preferential structural blocks in pharmacological probe designing with possibility of modifications at various positions on the core structure. Benzoxazolones showed various biological activities such as analgesics, anti-inflammatory and anti-cancer. Objective: In the present work, we have prepared new Mannich bases of 2(3H)-benzoxazolone derivatives and evaluated their cytotoxicities and proapoptotic properties in MCF-7 breast cancer cell line. Methods: The structures of these compounds were characterized by FT-IR, elemental analysis, 1H and 13C NMR. Cytotoxicities of all the target compounds were investigated by MTT assay. Apoptotic properties of compounds were evaluated by immunocytochemistry using antibodies against to caspase-3, cytochrome-c, FasL and TUNEL assay. Results: These two novel compounds, 1 and 2, both have the same piperazine substituent on the nitrogen atom of benzoxazolone and the main difference in the structures of these compounds is the presence of Cl substituent at the 5- position of the benzoxazolone ring. MTT results showed that compound 1 and 2 were effective in terms of reduction of cell viability at 100 µM and 50 µM concentration for 48 h, respectively. As a result of immunohistochemical staining, Fas L and caspase-3 immunoreactivities were significantly increased in MCF-7 cells after treated with compound 1. Additionally, caspase-3 and cytochrome-c immunoreactivities were also increased significantly in MCF-7 cells after treated with compound 2. The number of TUNEL positive cells was significantly higher in MCF-7 cells when compared with control group after treated with both compound 1 and 2. Conclusion: It could be concluded that N-substituted benzoxazolone derivatives increase potential anti-cancer effects and they could be promising novel therapeutic agents for chemotherapy.

Investigation of some 3-substituted-2(3H)-benzoxazolone derivatives against caspase-3 : A molecular docking study

“…According to Ivanova et al, chalcone compounds with benzoxazolone in their structure have antileukemic effects through triggering apoptotic cell death [11]. Furthermore, Erdag et al discovered that Mannich bases of benzoxazolone produced on the third position via Mannich reaction exhibit cytotoxic effects on the MCF-7 breast cancer cell line [12]. In the same study, it was reported that the chemical characteristics of the substituents at the fifth position of the benzoxazolone ring can affect the apoptotic cell pathways extrinsically or intrinsically.…”