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

PC Still; TF González-Cestari; L Pan; H Chai; JR Fuchs; T Ngoc Ninh; DD Soejarto; B Yi; BJ Henderson; DB McKay; AD Kinghorn

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

Abstract

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 IC₅₀values of 3–14µM; and inhibited activation of human α4β2 or α3β4 nicotinic receptors, showing IC₅₀values 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.)