title: Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents.
abstract: Harmine, a naturally occurring β-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of β-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure-activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities.
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang Xi Road, Guangzhou 510275, PR China. caorihui@mail.sysu.edu.cn
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Wenxi
authors.initials: W
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Guoxian
authors.initials: G
authors.lastname: Zhang
authors.forename: Jianru
authors.initials: J
authors.lastname: Li
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Ren
authors.forename: Liqin
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006247:Harmine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006247:Harmine