桦木醇和桦木酸 3-位修饰衍生物的生物活性及计算机模拟研究。

Biological Activity and In Silico Study of 3-Modified Derivatives of Betulin and Betulinic Aldehyde.

机构信息

Medical University of Silesia in Katowice, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Department of Organic Chemistry, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland.

Wroclaw University of Environmental and Life Science, Department of Experimental Biology, 27b Norwida Str., 50-375 Wrocław, Poland.

出版信息

Int J Mol Sci. 2019 Mar 19;20(6):1372. doi: 10.3390/ijms20061372.

A series of 3-substituted derivatives of betulin and betulinic aldehyde were synthesized as promising anticancer agents. The newly triterpenes were tested against five human cancer cell lines like biphenotypic B myelomonocytic leukaemia (MV-4-11), adenocarcinoma (A549), prostate (Du-145), melanoma (Hs294T), breast adenocarcinoma (MCF-7) and normal human mammary gland (MCF-10A). The compound showed towards Du-145, MCF-7 and Hs294T cells significant antiproliferative activity with IC ranging from 7.3 to 10.6 μM. The evaluation of ADME properties of all compounds also includes their pharmacokinetic profile. The calculated TPSA values for synthetized derivatives are in the range between 43.38 Å² and 55.77 Å² suggesting high oral bioavailability. The molecular docking calculations showed that triterpene fits the active site of the serine/threonine protein kinase Akt.

一系列桦木醇和桦木酸的 3-取代衍生物被合成作为有前途的抗癌药物。新的三萜类化合物被测试对五种人类癌细胞系，如双表型 B 髓单核白血病 (MV-4-11)、腺癌 (A549)、前列腺 (Du-145)、黑色素瘤 (Hs294T)、乳腺癌 (MCF-7) 和正常人类乳腺 (MCF-10A)。化合物对 Du-145、MCF-7 和 Hs294T 细胞具有显著的增殖抑制活性，IC 范围为 7.3 至 10.6 μM。所有化合物的 ADME 性质评估还包括它们的药代动力学特征。合成衍生物的计算 TPSA 值在 43.38 Å² 和 55.77 Å² 之间，表明具有较高的口服生物利用度。分子对接计算表明，三萜适合丝氨酸/苏氨酸蛋白激酶 Akt 的活性部位。