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新型吩噻嗪衍生物的合成:分子对接、对 PCS-201-012、HT-29 和 SH-SY5Y 细胞系的细胞毒性活性和氧化还原性质的评估。

Synthesis of new phenothiazine derivatives: Molecular docking, assessment of cytotoxic activity and oxidant-antioxidant properties on PCS-201-012, HT-29, and SH-SY5Y cell lines.

机构信息

Department of Chemistry, Faculty of Science, Gazi University, Ankara, Türkiye.

Department of Physiology, Faculty of Medicine, Kırklareli University, Kırklareli, Türkiye.

出版信息

Arch Pharm (Weinheim). 2024 Oct;357(10):e2400281. doi: 10.1002/ardp.202400281. Epub 2024 Jul 26.

DOI:10.1002/ardp.202400281
PMID:39058899
Abstract

Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC) values of compound 3a were determined to be 218.72, 202.85, and 227.86 μM while the IC values of compound 3b were defined to be 227.42, 199.27, and 250.11 μM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines.

摘要

吩噻嗪(PTZ)衍生物已被公认为多功能化合物,在医学的多个领域具有重要意义,特别是在癌症研究方面。合成化合物对正常细胞和癌细胞的细胞毒性作用及其氧化还原特性是癌症治疗策略的关键因素。在本研究中,合成了 8 种新的 PTZ 衍生物,并通过 3-[4,5-二甲基噻唑-2-基]-2,5 二苯基四氮唑溴盐(MTT)测定法评估了化合物的细胞毒性活性,同时通过氧化应激指数(OSI)计算评估了氧化还原特性在 SH-SY5Y(人神经母细胞瘤细胞系)、HT-29(人结肠直肠腺癌细胞系)和 PCS-201-012(人原代真皮成纤维细胞系)细胞中。结果表明,化合物 3a 的半最大抑制浓度(IC)值分别为 218.72、202.85 和 227.86μM,而化合物 3b 的 IC 值分别为 227.42、199.27 和 250.11μM在 PCS-201-012、HT-29 和 SH-SY5Y 细胞中。此外,与其他细胞系相比,合成的化合物在 PCS-201-012 细胞中表现出最低的 OSI。

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