Modification of Marine Natural Product Ningalin B and SAR Study Lead to Potent P-Glycoprotein Inhibitors
Chao Yang,
Iris L. K. Wong,
Wen Bin Jin,
Tao Jiang,
Larry M. C. Chow,
Sheng Biao Wan
Affiliations
Chao Yang
Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Iris L. K. Wong
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
Wen Bin Jin
Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Tao Jiang
Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Larry M. C. Chow
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
Sheng Biao Wan
Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
In this study, new marine ningalin B analogues containing a piperazine or a benzoloxy group at ring C have been synthesized and evaluated on their P-gp modulating activity in human breast cancer and leukemia cell lines. Their structure-activity relationship was preliminarily studied. Compounds 19 and 20 are potent P-gp inhibitors. These two synthetic analogues of permethyl ningalin B may be potentially used as effective modulators of P-gp-mediated drug resistance in cancer cells.
