Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Near East University, Nicosia, Cyprus.
Department of Biochemistry, Faculty of Pharmacy, Near East University, Nicosia, Cyprus.
Anticancer Agents Med Chem. 2021;21(1):84-90. doi: 10.2174/1871520620666200721125820.
2(3H)-Benzoxazolone derivatives are preferential structural blocks in pharmacological probe designing with the possibility of modifications at various positions on the core structure. Benzoxazolones showed various biological activities such as analgesics, anti-inflammatory and anti-cancer.
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.
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 caspase-3, cytochrome-c, FasL, and also TUNEL assay.
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 compounds 1 and 2 were effective in terms of reduction of cell viability at 100μM and 50μM concentration for 48h, respectively. As a result of immunohistochemical staining, Fas L and caspase-3 immunoreactivities were significantly increased in MCF-7 cells after treatment with compound 1. Additionally, caspase-3 and cytochrome-c immunoreactivities were also increased significantly in MCF-7 cells after treatment with compound 2. The number of TUNEL positive cells was significantly higher in MCF-7 cells when compared with the control group after treatment with both compounds 1 and 2.
It could be concluded that N-substituted benzoxazolone derivatives increase potential anti-cancer effects and they could be promising novel therapeutic agents for chemotherapy.
2(3H)-苯并恶唑酮衍生物是药理学探针设计中的首选结构模块，其核心结构的各个位置都有可能进行修饰。苯并恶唑酮具有多种生物活性，如镇痛药、抗炎药和抗癌药。
本工作制备了 2(3H)-苯并恶唑酮衍生物的新型曼尼希碱，并在 MCF-7 乳腺癌细胞系中评价了它们的细胞毒性和促凋亡特性。
通过 FT-IR、元素分析、1H 和 13C NMR 对这些化合物的结构进行了表征。通过 MTT 法测定所有目标化合物的细胞毒性。用 caspase-3、细胞色素 c、FasL 抗体和 TUNEL 法评价化合物的促凋亡特性。
这两个新化合物 1 和 2 在氮原子上都有相同的哌嗪取代基，这些化合物结构上的主要区别是苯并恶唑酮环 5 位上有 Cl 取代基。MTT 结果表明，化合物 1 和 2 在 100μM 和 50μM 浓度下分别作用 48h 后，均能有效降低细胞活力。免疫组织化学染色结果表明，化合物 1 处理后 MCF-7 细胞 FasL 和 caspase-3 免疫反应性明显增强。此外，化合物 2 处理后 MCF-7 细胞 caspase-3 和细胞色素 c 免疫反应性也明显增强。与对照组相比，用两种化合物处理后 MCF-7 细胞的 TUNEL 阳性细胞数明显增多。
N-取代苯并恶唑酮衍生物可增强潜在的抗癌作用，有望成为化疗的新型治疗药物。
