title: Evaluation of the anti-inflammatory and cytotoxic effects of anthraquinones and anthracenes derivatives in human leucocytes.
abstract: A variety of anthracene- and anthraquinone-related derivatives, modified from three types of lead structures, including 9-acyloxy 1,5-dichloroanthracene (type I), 1,5-bisacyloxy-anthraquinones with O-linked substituents (type II) and 1,5-bisacyloxy-anthraquinones with S-linked substituents (type III), were synthesized and evaluated by an in-vitro bioassay for their anti-inflammatory and cytotoxic effects in human leucocytes. Among these derivatives, type I compounds displayed potent anti-inflammatory activity against phorbol-12-myristate-13-acetate (PMA)-induced superoxide anion production, a bio-marker of inflammatory mediator production by neutrophils, with 50% inhibition (IC50) concentrations (microM) for compounds 1f, 1g, 1h and 1m being 13.8 +/- 3.0, 6.3 +/- 4.1, 33.2 +/- 1.3 and 33.9 +/- 5.7, respectively. Type II and type III derivatives (i. e., 1,5-bisacyloxy anthraquinone-related compounds) and the reference compound, emodin, exhibited relatively minor (20-40%) inhibitory effect against superoxide production by neutrophils. Furthermore, none of these compounds showed a significant cytotoxic effect in human neutrophils. In conclusion, these results suggest that compounds modified from 9-acyloxy 1,5-dichloroanthracence (type I) are more powerful than the other two types as anti-inflammatory drugs. This is the first demonstration that derivatives modified from anthracenes or anthraquinones possess anti-inflammatory activity with no significant cytotoxicity in human neutrophils.
authors.affiliation: Department & Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Chen
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
authors.forename: Jyh-Fei
authors.initials: JF
authors.lastname: Liao
authors.forename: Li-Kang
authors.initials: LK
authors.lastname: Ho
authors.forename: Yueh-Ching
authors.initials: YC
authors.lastname: Chou
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Wang
authors.forename: Chieh-Fu
authors.initials: CF
authors.lastname: Chen
mesh_terms: D000873:Anthracenes / Q000494:pharmacology*; D000880:Anthraquinones / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors*
chemical_list: D000873:Anthracenes; D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D013481:Superoxides