Abstract
Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC(50) values of 0.9 and 0.8 μg/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / pharmacology
-
Apoptosis / drug effects
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
Drug Resistance, Multiple
-
Drug Resistance, Neoplasm
-
Drug Screening Assays, Antitumor
-
Humans
-
Inhibitory Concentration 50
-
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
-
Neutrophils / drug effects
-
Neutrophils / metabolism
-
Pancreatic Elastase / antagonists & inhibitors
-
Pancreatic Elastase / metabolism
-
Prenylation
-
Structure-Activity Relationship
-
Superoxides / metabolism
-
Xanthones / chemical synthesis*
-
Xanthones / pharmacology
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Antineoplastic Agents
-
Xanthones
-
Superoxides
-
N-Formylmethionine Leucyl-Phenylalanine
-
gambogic acid
-
Pancreatic Elastase