title: In-vitro antitumor activity evaluation of hyperforin derivatives.
abstract: The derivatives of hyperforin, namely hyperforin acetate (2), 17,18,22,23,27,28,32,33-octahydrohyperforin acetate (3), and N,N-dicyclohexylamine salt of hyperforin (4), have been investigated for their antitumor properties. In-vitro studies demonstrated that 2 and 4 were active against HeLa (human cervical cancer), A375 (human malignant melanoma), HepG2 (human hepatocellular carcinoma), MCF-7 (human breast cancer), A549 (human nonsmall cell lung cancer), K562 (human chronic myeloid leukemia), and K562/ADR (human adriamycin-resistant K562) cell lines with IC(50) values in the range of 3.2-64.1 μM. The energy differences between highest occupied molecular orbital and lowest unoccupied molecular orbital of 2-4 were calculated to be 0.39778, 0.43106, and 0.30900 a.u., respectively, using the Gaussian 03 software package and ab initio method with the HF/6-311 G* basis set. The result indicated that the biological activity of 4 might be the strongest and that of 3 might be the weakest, which was in accordance with their corresponding antiproliferative effects against the tested tumor cell lines. Compound 4 caused cell cycle arrest at G2/M phase in flow cytometry experiment and induced apoptosis by 4',6-diamidino-2-phenylindole staining and Annexin V-FITC/PI (propidium iodide) double-labeled staining in HepG2 cells. The results indicated a potential for N,N-dicyclohexylamine salt of hyperforin as a new antitumor drug.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Jin-Yun
authors.initials: JY
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
authors.forename: De-Po
authors.initials: DP
authors.lastname: Yang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013729:Terpenes; C455159:hyperforin acetate; C560957:hyperforin, N,N-dicyclohexylamine salt; D010696:Phloroglucinol; C001654:hyperforin