Planta Med 2012; 78 - CL11
DOI: 10.1055/s-0032-1320246

Alkaloids from Grewia Paniculata with cytotoxic and non-competitive nicotinic receptor antagonistic activities

PC Still 1, TF González-Cestari 2, L Pan 1, H Chai 1, JR Fuchs 1, T Ngoc Ninh 3, DD Soejarto 4, B Yi 2, BJ Henderson 2, DB McKay 2, AD Kinghorn 1
  • 1Division of Medicinal Chemistry and Pharmacognosy
  • 2Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210
  • 3Institute of Ecology and Biological Resources, Vietnamese Academy of Science and Technology, Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
  • 4Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612

Grewia paniculata Roxb. ex DC. (Malvaceae) (voucher specimen: Soejarto et al. 14261) is a shrub or small tree that grows in Southeast Asia. Three new piperidine alkaloids, microgrewiapines A-C, and nine known compounds, were isolated from separate chloroform-soluble extracts of the stem bark, roots and leaves of G. paniculata. Microgrewiapines A-C showed inhibition of the growth of the HT-29 human colon cancer cell line with IC50 values of 3–14µM; and inhibited activation of human α4β2 or α3β4 nicotinic receptors, showing IC50 values in the low micromolar range. As a result of these studies, microgrewiapine A was found to be selectively cytotoxic, with noncompetitive inhibitory nicotinic receptor activity. This study represents the first report of cytotoxic and CNS modulatory piperdine alkaloids from genus Grewia. (Supported, in part, by grant P01 CA125066 from NCI/NIH.)