派罗尼酮及其苯甘氨酸衍生物通过半胱天冬酶诱导人神经胶质瘤细胞的细胞毒性。

Perezone and its phenyl glycine derivative induce cytotoxicity via caspases on human glial cancer cells.

机构信息

Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu SN, U. A. Zacatenco, Ciudad de México, México.

Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Ciudad de México, México.

出版信息

Nat Prod Res. 2024 Jun;38(11):1823-1833. doi: 10.1080/14786419.2023.2225121. Epub 2023 Jun 21.

DOI:10.1080/14786419.2023.2225121

PMID:37341748

Abstract

The new phenyl glycine derivative of perezone was obtained in a single reaction step in . 80% yield which showed remarkable cytotoxic activity against the astrocytoma U-251 cell line. After 24 h of exposure, both perezone (IC = 6.83 ± 1.64 µM) and its phenyl glycine derivative (2.60 ± 1.69 µM) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC = 28.54 ± 1.59 and 31.87 ± 1.54 µM respectively). Both compounds induced cellular morphological changes (pyknosis or cytoplasmic vacuolization) and increased the expression of caspases 3, 8, and 9 genes related to apoptosis. In the acute toxicity study, phenyl glycine perezone (DL = 2000 mg/Kg) demonstrated to be less toxic than perezone (DL = 500 mg/Kg). Phenylglycine-perezone can envisage a beneficial therapeutic potential.

摘要

新型苯甘氨酸衍生物派热醇在一步反应中以 80%的收率得到，对星形细胞瘤 U-251 细胞系表现出显著的细胞毒性活性。暴露 24 小时后，派热醇（IC = 6.83 ± 1.64 μM）及其苯甘氨酸衍生物（2.60 ± 1.69 μM）对 U-251 细胞均表现出细胞毒性作用，但对非肿瘤 SVGp12 细胞系的细胞毒性低 5 倍（IC = 28.54 ± 1.59 和 31.87 ± 1.54 μM）。两种化合物均诱导细胞形态发生变化（固缩或细胞质空泡化），并增加与细胞凋亡相关的 caspase 3、8 和 9 基因的表达。在急性毒性研究中，苯甘氨酸派热醇（DL = 2000 mg / Kg）的毒性比派热醇（DL = 500 mg / Kg）低。苯甘氨酸-派热醇可能具有有益的治疗潜力。