Abstract：
The phytochemical analysis of ethyl acetate and methanol extract of Goniothalamus wynaadensis Bedd. leaves led to an isolation of eight (1-8) known molecules, among them seven (2-8) isolated for the first time from this species, which includes (+)-goniothalamin oxide (2), goniodiol-7-monoacetate (3), goniodiol-8-monoacetate (4), goniodiol (5), (+)-8-epi-9-deoxygoniopypyrone (6) etc. The phytochemical modification by acetylation of 3 and 4 gave goniodiol diacetate (9) with absolute configuration (6R, 7R, 8R) confirmed by single crystal X-ray diffraction. Compounds 3-9 were cytotoxic against breast, ovarian, prostate and colon cancer cell lines with IC50 <10 μM. Cell cycle analysis and Annexin-V assay on MDA-MB-231 cell using goniodiol-7-monoacetate (3) exhibited apoptotic response as well as necrotic response and showed cell proliferation arrest at G2/M phase. An in silico target identification for these molecules was carried out with an α-tubulin protein target by covalent docking. To gain an in-depth understanding and identify the stability of these protein-ligand complexes on thermodynamic energy levels, further assessment of the isolated molecules binding to the Cys-316 of α-tubulin was performed based on reaction energetic analysis via DFT studies which hinted the isolated molecules may be α-tubulin inhibitors similar to Pironetin. Molecular dynamics reiterated the observations.
摘要：
金丝雀乙酸乙酯和甲醇提取物的植物化学分析。叶子导致八种（1-8）已知分子的分离，其中七（2-8）首次从该物种中分离出来，其中包括（+）-氧化淋胺（2），goniodiol-7-单乙酸酯（3），goniodiol-8-单乙酸酯（4），goniodiol(5),(+)-8-epi-9-脱氧吡喃酮(6)等..通过3和4的乙酰化进行的植物化学修饰得到了具有绝对构型（6R，7R,8R)经单晶X射线衍射证实。化合物3-9对乳腺有细胞毒性，卵巢,前列腺癌和结肠癌细胞系，IC50<10μM。使用gonioidol-7-单乙酸盐(3)对MDA-MB-231细胞的细胞周期分析和膜联蛋白-V测定表现出凋亡反应以及坏死反应,并显示在G2/M期的细胞增殖停滞。通过共价对接用α-微管蛋白靶标进行这些分子的计算机靶标鉴定。为了深入了解并确定这些蛋白质-配体复合物在热力学能级上的稳定性，基于通过DFT研究的反应能量分析,对与α-微管蛋白的Cys-316结合的分离分子进行进一步评估,该研究提示分离分子可能是类似于Pironetin的α-微管蛋白抑制剂。分子动力学重申了这些观察结果。
