Abstract

A novel triterpenoid, holarol(1),3β-lup-20(31)-en-3,29,30-triol along with one seco-triterpenoid, dihydrocanaric acid(2) and one known pentacyclic triterpenoid, betulin(3) have been isolated from Holarrhena antidysenterica (L.)Wall. (Family: Apocynaceae). The structures of the compounds were elucidated by extensive IR, 1D, 2D NMR and mass spectrometric analysis. The optimised geometry of (1) was calculated by density-functional theory (DFT) using M06-2X hybrid functional and 6–31 G(D) basis set. The compounds showed differential cytotoxic activities in the cell lines-HeLa, EAC, Raji and T24. Seco-triterpenoid (2) showed highest sensitivity (IC₅₀: 1.710 μg/mL) against the bladder cancer cell line T24 followed by (1) (IC₅₀ 9.698 µg/mL) and (3) (IC₅₀ 11.769 µg/mL). Compound (1) showed highest reactive oxygen species (ROS) generation in T24 cell line followed by (3) and (2) resulting in induction of apoptosis through activation of caspase, cleavage of PARP and reduction of Bcl-2/Bax ratio. Thus compounds (1), (2) along with (3) could be potent anticancer agents.

摘要

一种新型的三萜类化合物，holarol （1），3β-LUP-20（31）具有一个沿烯3,29,30三醇seco-三萜，dihydrocanaric酸（2）和一个已知的五环三萜，桦木醇（3）有从Holarrhena antidysenterica (L.)Wall 中分离出来。（科：夹竹桃科）。通过广泛的红外、一维、二维核磁共振和质谱分析阐明了化合物的结构。(1)的优化几何是通过密度泛函理论 (DFT) 计算的，使用 M06-2X 混合泛函和 6-31 G(D) 基组。这些化合物在 HeLa、EAC、Raji 和 T24 细胞系中显示出不同的细胞毒活性。山仲三萜(2)对膀胱癌细胞系 T24表现出最高的敏感性 (IC ₅₀ : 1.710 µg/mL)，其次是(1) (IC ₅₀ 9.698 µg/mL) 和(3) (IC ₅₀ 11.769 µg/mL)。化合物(1)在 T24 细胞系中显示出最高的活性氧 (ROS) 生成，其次是(3)和(2)导致通过激活半胱天冬酶、裂解 PARP 和降低 Bcl-2/Bax 比率诱导细胞凋亡。因此化合物(1)、(2)连同(3)可能是有效的抗癌剂。