Xanthorrhizol and its derivatives as the inhibitors of caspase-7
Yunita Purnamasari, Nizar Happyana, Yana Maolana Syah*

Department of Chemistry, Bandung Institute of Technology

Abstract

Xanthorrhizol (1) is a bisabolene sesquiterpene found as the main terpenoid constituent of the Curcuma xanthorrhiza rhizomes. The compound is reported to having a range of biological activities, including as anti-estrogenic, anti-estrogenic, anti-inflammatory, antioxidant, anti-hyperglycemic, nephroprotective, and hepatoprotective properties. Although the biological properties of 1 has a low selectivity, this fact showed that 1 has the potential as a bioactive molecule. To increase its selectivity, as well as to be more potent its biological properties, we had synthesize six derivatives of 1 using a number of chemical reactions, including nitration (followed by nitro reduction) and substitution reactions. The nitration reaction resulted two isomer ic nitroderivatives, namely 2-nitroxanthorrhizol (2) and 4-nitroxanthorrhizol (3). Reducing of 2 by acetic acid yielded 2-aminoxanthorrhizol (4). In the substitution reaction of the phenolic-OH group afforded 4-(3-(2-methyl-5-(6-methylhept-5-en-2-yl)phenoxy)propyl)morpholine (5), 6,7-dimethoxy-3-(3-(2-methyl-5-(6-methyilhept-5-en-2-yl)phenoxy)propyl)quinazoline-4(3H)-on (6), and N-benzyl-3-(2-methyl-5-(6-methylhept-5-en-2-yl)phenoxy)propane-1-amine (7). The structures of these derivatives were determined analyzing their NMR and mass spectral data. Compounds 1-6 were tested for their capacity to inhibit caspase-7, the enzyme that responsible for a diverse physiological and cell-damaging stressors and delaying the onset of apoptosis. The results showed that only 2 and 3 that can weakly inhibit the enzyme activity (~ 15% inhibition). In conclusion, six derivatives had been synthesized from xanthorrhizol (1), which only the derivatives 2 and 3 that showed inhibition to the caspase-7.

Keywords: Synthesis, Xanthorrhizol, Cancer, Caspase-7

Topic: Organic Synthesis and Medicinal Chemistry