Synthesis of novel rhinacanthins and related anticancer naphthoquinone esters.
Rhinacanthin-M, -N and -Q, natural products isolated from the medicinal plant Rhinacanthus nasutus, and 39 novel naphthoquinone esters have been synthesized in excellent yield by esterification of naphthoquinone-3-(propan-3'-ols) with benzoic or naphthoic acids. Almost all the naphthoquinone esters that contain a C-3 hydroxy group showed significant cytotoxicities against KB, HeLa, and HepG2 cell lines. In contrast, ester derivatives lacking the C-3 hydroxy group were inactive to the cancer cell lines. Two methyl substituents on the C-2' of propyl chain conferred more potent cytotoxicity than when there is only one or no methyl group. Naphthoate esters exhibited greater cytotoxicity than benzoate esters. Computer modeling has been done to obtain a first look at the mode of action in connection with these observations.
Kongkathip
Ngampong
N
Natural Products and Organic Synthesis Research Unit (NPOS), Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. fscinpk@ku.ac.th
Luangkamin
Suwaporn
S
Kongkathip
Boonsong
B
Sangma
Chak
C
Grigg
Ronald
R
Kongsaeree
Palangpon
P
Prabpai
Samran
S
Pradidphol
Narathip
N
Piyaviriyagul
Suratsawadee
S
Siripong
Pongpun
P
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D004952:Esters; D009285:Naphthoquinones; D059005:Topoisomerase II Inhibitors; C117115:rhinacanthin Q; D004317:Doxorubicin