Nyandoro Stephen S, Munissi Joan J E, Gruhonjic Amra, Duffy Sandra, Pan Fangfang, Puttreddy Rakesh, Holleran John P, Fitzpatrick Paul A, Pelletier Jerry, Avery Vicky M, Rissanen Kari, Erdélyi Máté
Department of Chemistry, College of Natural and Applied Sciences, University of Dar es Salaam , P.O. Box 35061, Dar es Salaam, Tanzania.
Department of Chemistry and Molecular Biology, University of Gothenburg , SE-412 96 Gothenburg, Sweden.
J Nat Prod. 2017 Jan 27;80(1):114-125. doi: 10.1021/acs.jnatprod.6b00759. Epub 2016 Dec 21.
Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC values of 0.2-40 μM, and against HEK293 mammalian cells (IC 2.7-3.6 μM). While the crude extract was inactive at 100 μg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC values ranging from 0.03-8.2 μM. Compound 1 showed the most potent antiplasmodial (IC 0.2 μM) and cytotoxic (IC 0.03 μM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 μM.
从基氏闭壳花椒（Cleistochlamys kirkii）叶片的甲醇提取物中分离出13种新的代谢产物，包括多羟基环己烯衍生物闭壳花椒二醇（1）、闭壳花椒烯醇B（3）、闭壳花椒氯醇A（4）和B（5）、闭壳花椒二醇A - F（6 - 11）、闭壳花椒烯酮（12）以及丁烯内酯闭壳花椒内酯（13）、2,5 - 二羟基苄基苯甲酸酯（闭壳花椒酚内酯，14），还有8种已知化合物（2, 15 - 21）。通过核磁共振光谱和质谱分析对纯化后的代谢产物进行了鉴定，而化合物1、17和19的绝对构型则通过单晶X射线衍射确定。基于化合物2的核磁共振光谱特征和旋光性与化合物1（其构型通过X射线衍射确定）的比较，修正了化合物2的环外双键构型。观察到基氏闭壳花椒中环己烯类化合物和庚烯内酯的共存具有生源合成和化学分类学意义。一些分离出的化合物对恶性疟原虫（3D7、Dd2）表现出活性，IC值为0.2 - 40 μM，对人胚肾293（HEK293）哺乳动物细胞也有活性（IC 2.7 - 3.6 μM）。虽然粗提物在100 μg/mL时对MDA - MB - 231三阴性乳腺癌细胞系无活性，但其一些分离成分表现出细胞毒性活性，IC值范围为0.03 - 8.2 μM。化合物1表现出最强的抗疟活性（IC 0.2 μM）和细胞毒性活性（IC 0.03 μM，MDA - MB - 231细胞系）。所研究的化合物在20 μM时均未表现出体外翻译抑制活性。
