School of Pharmacy, Hangzhou Normal University, Hangzhou, China.
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Hangzhou, China.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2403-2416. doi: 10.1080/14756366.2022.2117314.
A series of novel -alkyl--hydroxyl carboximates derived from -elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound -elemene (). Notably, compound exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound could significantly induce cell apoptosis. Further study in the H460 xenograft mouse model validated the anti-tumour activities of with a greater tumour growth inhibition (TGI, 68.3%) than -elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such -alkyl--hydroxyl carboximate class of compounds exemplified as demonstrated potent anticancer activities both and , and should warrant further investigation for potential anticancer therapy.
一系列新型的-烷基--羟基羧酸酯衍生物是从榄香烯偶然发现的。它们中的大多数表现出比其先导化合物榄香烯（）更强的抗增殖活性。值得注意的是，化合物对三种肺癌细胞系（H1975、A549 和 H460）和其他几种肿瘤细胞系（H1299、U87MG、MV4-11 和 SU-DHL-2）的增殖具有显著的抑制作用。初步的机制研究表明，化合物可以显著诱导细胞凋亡。在 H460 异种移植小鼠模型中的进一步研究验证了化合物在 60mg/kg ip 剂量下的抗肿瘤活性，与榄香烯和 SAHA 相比，肿瘤生长抑制（TGI，68.3%）更大，分别为 50.1%和 55.9%，没有明显的体重减轻和毒性。因此，这种-烷基--羟基羧酸酯类化合物，如化合物所示，表现出强大的抗癌活性，值得进一步研究用于潜在的癌症治疗。
