Cytotoxic dimeric quinolone–terpene alkaloids from the root bark of Zanthoxylum rhetsa Monira Ahsan a , Mohammad Rashedul Haque a , Md. Belayet Hossain a , Sheikh Nazrul Islam b , Alexander I. Gray c , Choudhury Mahmood Hasan a,⇑ a Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh b Institute of Nutrition and Food Science, University of Dhaka, Dhaka 1000, Bangladesh c Department of Pharmaceutical Sciences, University of Strathclyde, SIBS Building, 27 Taylor Street, Glasgow G4 ONR, UK article info Article history: Received 24 August 2013 Received in revised form 6 February 2014 Available online 22 April 2014 Keywords: Chelerybulgarine Dihydrochelerythrine 2 0 -Episimulanoquinoline 2,11-Didemethoxyvepridimerine Rhetsidimerine abstract Four quinolone–terpene alkaloids, chelerybulgarine (1), 2 0 -episimulanoquinoline (3), 2,11-didemethoxy- vepridimerine B (4), and rhetsidimerine (5) were isolated from the root bark of Zanthoxylum rhetsa DC. Chelerybulgarine (1) is a C–C linked terpene alkaloid where the C-6 of dihydrochelerythrine is linked to C-11 of the sesquiterpenoid 10b-methoxybulgarene. 2 0 -Episimulanoquinoline is a dimeric alkaloid containing dihydrochelerythrine and 8-methoxy-N-methylflindersine moieties, whereas 2,11-didemethoxyvepridimerine B and rhetsidimerine are dimeric prenylated quinolone alkaloids. Seven of the isolated compounds exhibited weak cytotoxicity when tested against a panel of six human stomach-cancer cell lines. Ó 2014 Elsevier Ltd. All rights reserved. Introduction Zanthoxylum rhetsa DC (Syn. Zanthoxylum budrunga; Bengali name, Bazna; Family, Rutaceae) is a medium-sized tree with pale, corky bark that grows in Bangladesh, India, Myanmar, Thailand, Malaysia and other tropical countries. The fruits and stem bark are used in the treatment of asthma, bronchitis, heart complaints and rheumatism. The essential oil is used to treat cholera and as an antiseptic and disinfectant (Yusuf et al., 1994). A number of alkaloids, including canthine-6-one (Ahsan et al., 2001), 8-meth- oxy-N-methylfindersine (Ahsan et al., 2000), dihydrochelerythrine (Ahsan et al., 2001), chelerythrine, rhetine, rhetsine, rhetsinine (Chatterjee et al., 1959), dihydroavicine (Joshi et al., 1991), dictam- nine, arborine (Ruangrungsi et al., 1981) and others have been iso- lated from the stem bark of the plant. In addition, reports have identified the coumarins suberosin (Ewing et al., 1950) and xan- thyletin as well as the lignin esamin in the plant (Ahsan et al., 2000). The essential oil of the fruit and seed contains mainly mon- oterpenoids (Jirovetz et al., 1998; Shankaracharya et al., 1994). We report the isolation and structural elucidation of five dimeric alkaloids, including four new quinolone–terpene alkaloids, from Z. rhetsa. In addition, we isolated two known alkaloids, three lignans, and lupeol. The methanol extraction of Z. rhetsa root bark produced compounds 1–5, 8-methoxy-N-methylflindersine (Ahsan et al., 2000), rhetsine (evodiamine) (Chatterjee et al., 1959), piperitol-c, c-dimethylallyl ether, xanthoxylol-c,c-dimethylallyl ether (Fumiko et al., 1973), sesamin (Nissanka et al., 2001), and lupeol. N O N O O O H 3 CO CH 3 CH 3 OCH 3 1 2 4 5 6 7 8 10 11 13 19 15 16 17 18 4a 4b 7a 6a 9a 13a 13b 16b 18a H e H f H g H c N O O CH 3 OCH 3 H 3 CO 1 2 4 5 6 7 8 10 11 4a 4b 6a 10a 10b 12 12a H OCH 3 H H 1 1' 3' 5' 6' 8' 10' 11' 13' 14' N O O O N O OCH 3 CH 3 OCH 3 H 3 CO CH 3 H 1' 2' 4' 5' 6' 7' 8' 10' 4'a 6a 10' b 10'a 1 2 4 4a 4b 5 6 6a 7 9 10 10a 11 12 2 3 4 H a Hb 1 2 4 5 6 7 8 10 11 13 14 15 16 17 18 19 20 21 4a 4b 10b 12a 11' N O O O N O OCH 3 CH 3 OCH 3 H 3 CO CH 3 H 1' 2' 4' 5' 6' 7' 8' 10' 4'a 6a 10' b 10'a 1 2 4 4a 4b 5 6 6a 7 9 10 10a 11 12 10b 12a 11' 14 N O N H 3 C CH 3 H3CO OCH 3 O O O H b H a H f H d Hc H e 6a 7a 9 9a 13a 13b 16a 5 H g H d H http://dx.doi.org/10.1016/j.phytochem.2014.03.008 0031-9422/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Mobile: +880 1819253698; fax: +880 2 8615583. E-mail address: cmhasan@gmail.com (C.M. Hasan). Phytochemistry 103 (2014) 8–12 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem