Oxyresveratrol: Structural Modification and Evaluation of Biological Activities.
Oxyresveratrol (2,4,3',5'-tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic aromatic substitution. The two aromatic rings of the stilbene system of 1 can be chemically modulated by exploiting different protecting groups. Such a strategy allows for selective and exclusive modifications on either ring A or ring B. All compounds were evaluated in vitro for a panel of biological activities, including free radical scavenging activity, DNA protective properties, antiherpetic activity, inhibition of α-glucosidase and neuraminidase, and cytotoxicity against some cancer cell lines. Several derivatives were comparably active or even more potent than the parent oxyresveratrol and/or the appropriate positive controls. The partially etherified analogs 5'-hydroxy-2,3',4-trimethoxystilbene and 3',5'-dihydroxy-2,4-dimethoxystilbene demonstrated promising anti-herpetic and DNA protective activities, offering new leads for neuropreventive agent research, whereas 5'-hydroxy-2,3',4,-triisopropoxystilbene displayed anti-α-glucosidase effects, providing a new lead molecule for anti-diabetic drug development. 3',5'-Diacetoxy-2,4-diisopropoxystilbene showed potent and selective cytotoxicity against HeLa cancer cells, but the compound still needs further in vivo investigation to verify its anticancer potential.
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. manee_many@hotmail.com.
Nutputsorn
N
Chatsumpun
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. s_taksina@yahoo.com.
Taksina
T
Chuanasa
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Boonchoo.Sr@chula.ac.th.
Boonchoo
B
Sritularak
Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Vimolmas.L@chula.ac.th.
Vimolmas
V
Lipipun
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Vichien.J@chula.ac.th.
Vichien
V
Jongbunprasert
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, and Program in Chemical Biology, Chulabhorn Graduate Institute, 54 Kampaeng Phet 6 Road, Bangkok 10210, Thailand. somsak@cri.or.th.
Somsak
S
Ruchirawat
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, and Program in Chemical Biology, Chulabhorn Graduate Institute, 54 Kampaeng Phet 6 Road, Bangkok 10210, Thailand. poonsakdi@cri.or.th.
Poonsakdi
P
Ploypradith
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Kittisak.L@chula.ac.th.
Kittisak
K
Likhitwitayawuid
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D010936:Plant Extracts; D013267:Stilbenes; C034912:puag-haad
Artocarpus lacucha; Artocarpus lakoocha; cytotoxicity; free radicals; herpes simplex; oxyresveratrol; stilbene; α-glucosidase