title: Design, synthesis and in vitro evaluation of novel dehydroabietic acid derivatives containing a dipeptide moiety as potential anticancer agents.
abstract: A series of novel dehydroabietic acid (DHA) chiral dipeptide derivatives were designed and synthesized as potent antitumor agents. The inhibitory activities of these compounds against NCI-H460 (lung), HeLa (epithelial cervical) and MGC-803 (gastric) human cancer cell lines were estimated by MTT assay in vitro. The antitumor activities screening indicated that many compounds showed moderate to high levels of antitumor activities against these three cancer cell lines and most of these compounds displayed more potent inhibitory activities compared with commercial anticancer drug 5-fluorouracil (5-FU). The induction of apoptosis and affects on the cell cycle distribution with compound 8k were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, flow cytometry and the activities of caspase-3 and -9 assay in Hela cells, which exhibited that the compound could induce cell apoptosis in Hela cells. In addition, further investigation showed that apoptosis were associated with loss of mitochondrial membrane potential, enhancement of mitochondrial cytochrome c release and intracellular ROS production, elevation of Bax expression, down-regulation of Bcl-2, and the activation of caspase-9 and -3.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Xiao-Chao
authors.initials: XC
authors.lastname: Huang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Le
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China; Department of Chemistry and Pharmaceutical Science, Guilin Normal College, Xinyi Road 21, Guangxi 541001, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China. Electronic address: panym2013@hotmail.com.
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Pan
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China. Electronic address: whengshan@163.com.
authors.forename: Heng-Shan
authors.initials: HS
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D004151:Dipeptides; D017382:Reactive Oxygen Species; C013913:dehydroabietic acid; D045304:Cytochromes c
keywords: Antitumor; Apoptosis; Chiral; Dehydroabietic acid; Dipeptide