New Alkaloids from Pancratium maritimum Sabrin R. M. Ibrahim 1 , Gamal A. Mohamed 2, 3 , Lamiaa A. Shaala 4 , Diaa T. A. Youssef 2, 5 , Khalid A. El Sayed 6 1 Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, Egypt 2 Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia 3 Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt 4 Suez Canal University Hospital, Suez Canal University, Ismailia, Egypt 5 Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt 6 Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA Abstract ! As a part of ongoing search efforts for the discovery of anticancer lead entities from natural sources, bulbs and flowers of the amar- yllidaceous plant Pancratium maritimum have been investigated. Fractionation of the extracts of the fresh flowers and bulbs of P. maritimum led to the isolation of four new alkaloids, namely pan- crimatines A (1) and B (2), norismine (3), and pancrimatine C (4), together with the previously reported N-methyl-8,9-methyl- enedioxy-6-phenanthridone (5), trispheridine (6), and N-meth- yl-8,9-methylenedioxyphenanthridine (7). The structures of these alkaloids were established on the basis of extensive 1D and 2D NMR and high-resolution mass spectral analyses as well as comparison with the literature. Compounds 2 and 7 showed antiproliferative and antimigratory activity against the highly metastatic human prostate cancer cell line PC-3 cells without cy- totoxicity. The phenanthridine alkaloid class was identified as having potential for use to control prostate cancer proliferation and migration. Key words Amaryllidaceae · Pancratium maritimum · alkaloids · antimi- gratory · antiproliferative activity Supporting information available online at http://www.thieme-connect.de/ejournals/toc/plantamedica The Amaryllidaceae family compromises about 65 genera with about 1100 species widely distributed throughout the tropical and warm temperature regions of the world [1]. It represents one of the 20 most important alkaloid-containing plant families [2]. Bulb and flower extracts of Pancratium maritimum L. possess purgative, acaricidal, insecticidal, antiviral, antimicro- bial, immunostimulant, analgesic, antitumor, antifungal, and antimalarial activities [3–8]. Considerable attention has been giv- en to the genus Pancratium due to the unique and complex struc- tural types of its alkaloids. The most widely known compounds of this group, narciclasine, lycoricidine, pancratistatin, and their congeners have demonstrated potent in vitro cytotoxicity against cancer cell lines and potent in vivo antitumor activity [9–11]. The oil from Narcissus species (Amaryllidaceae) is already being used successfully for the treatment of cancer [10, 11]. Earlier investiga- tion of the Egyptian collection of P. maritimum L. resulted in the isolation of alkaloids [6, 12], together with non-alkaloidal classes of compounds such as chromones, flavonoids, and acetophe- nones [13]. This study reports the isolation and structural elucidation of two new alkaloids; pancrimatine A (1) and pancrimatine B (2) from the polar n-BuOH fraction of the fresh bulbs of the plant. More- over, the new alkaloids norismine (3) and pancrimatine C (4), to- gether with the previously reported alkaloids N-methyl-8,9- methylenedioxy-6-phenanthridone (5) [14], trispheridine (6) [14], and N-methyl-8,9-methylenedioxyphenanthridine (7) [14], were isolated from the fresh flowers. These alkaloids were as- signed by extensive spectroscopic methods. The known alkaloids were identified by comparison of their spectroscopic and physi- cal data with the literature (l " Fig. 1). The isolated compounds were evaluated for their cytotoxic activity using brine shrimp, wound healing, and MTT assays. Pancrimatine A (1) is a phenanthridone-alkaloid, belonging to the narciclasine skeleton group, which is a common group among Fig. 1 Chemical structures of the isolated com- pounds. 1480 Ibrahim SRM et al. New Alkaloids from … Planta Med 2013; 79: 1480–1484 Letters Downloaded by: Food and Drug Administration (FDA). Copyrighted material.