Synthesis of Novel Rhinacanthins and Related Anticancer Naphthoquinone Esters

• Published in: Journal of medicinal chemistry 2004-08, Vol.47 (18), p.4427-4438
• Main Authors: Kongkathip, Ngampong, Luangkamin, Suwaporn, Kongkathip, Boonsong, Sangma, Chak, Grigg, Ronald, Kongsaeree, Palangpon, Prabpai, Samran, Pradidphol, Narathip, Piyaviriyagul, Suratsawadee, Siripong, Pongpun
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding Sites; Biological and medical sciences; Cell Division - drug effects; Cell Line, Tumor; Doxorubicin - chemistry; Esters - chemical synthesis; Esters - pharmacology; General aspects; General pharmacology; Humans; Inhibitory Concentration 50; Medical sciences; Models, Molecular; Naphthoquinones - chemical synthesis; Naphthoquinones - pharmacology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Rhinacanthus nasutus; Structure-Activity Relationship; Topoisomerase II Inhibitors
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm030323g

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.