Journal of Natural Products Vol. 51, No. 3 , pp. 599-600, Maydun 1988
5 99
JUSTICIDINB,A CYTOTOXIC PRINCIPLE FROMJUSTZCZA PECTORALZS H. JOSEPH,J. G u n , * C. MOWS, Laboratoire de Phatnkuognosie, Faculti du Sciences Phatnkueutiques, 3 1 Allies Jules Gmak, Uniuersiti Toulouse 111, F-3 1400 Touloure, France
L.J. MENSAH, Labwatoire de Pharmacognosie, Facultide Pharmacie, Uniwrsiti d'Abidjan, 01 B P V34 Abidjan, Republique de Cite dlvoire C. ROUSAKIS, and C. GRATAS
Laboratoire de Recherrhe Thkapeutiqueen Cawindogie, UFR de Miderne et Techniques Midicales, 1 rue Gaston Veil, F-44035 Nantcs Cedex, France
Justicia peFtoralis Jacq. (Acanthaceae), a native to tropical America, is used in folk medicine for several diseases. Decoctions of the whole plant are used by Puinave Indians to treat pulmonary infections (1). In Central America and the West Indies, it is used to relieve cough and as an expectorant or sudorific (2,3). Also, leaves, mixed with bark resin of Virola species, were used as an ingredient in hallucinogenic snuff ( 4 ) . The presence of coumarins and the absence of lignans from J . pectoralis var. stenophylla Leon. collected in Peru have been reported ( 4 ) . We report the isolation of a l-aryl2,3-naphthalide lignan (justicidin B) from J . pectoralis samples collected in French Guyana. This lignan is known in several other AsiaticJusticia species ( 5 , G ) and other sources such as Phyllanthus (Euphorbiaceae) (7) and Sesbania (Fabaceae) ( 8 ) .Justicidin B has been found to be active in vitro (9PS ED,, 3 . 3 pg/ml, 9KB ED5, 7.3 X and 1.2 X pg/ml) (7,8), but invitro cytotoxicity in NSCLCNG (bronchial epidermoid carcinoma cell line of human origin) (9) has not been reported. We found activity in NCI murine P-388 lymphocytic leukemia (PS system) comparable to published results (7), but the compound is weakly active in NSCLCNG. EXPERIMENTAL F"TMATERIAL.-J. pectoralis was collected
in French Guyana in June 1984. Voucher specimens are deposited in the Herbarium of the FacultC des Sciences Pharmaceutiques, UnivenitC Toulouse 111, France. EXTRACTIONAND ISOLATION OF JUSTICIB.-Dried, whole plants (600 g) were Soxhlet extracted with EtOH. The EtOH residue was chromatographed on an Amberlite XAD2 column with MeOH/H,O mixtures of decreasing polarity. The MeOH-H,O (80:20) fraction furnished justicidin B that was purified by chromatography on Si gel with CHC1,-MeOH (98:2) followed by centrifugal circular tlc on Si gel with hexane-EtOAc (95:5). Justicidin B (53 mg) was washed with MeOH and then crystallized from cyclohexane. Justicidin B was compared with an authentic sample (mp, uv, ir, 'H nmr, ms) isolated from Pbyllanthus subglmatur (10). DIN
BIOLOGICALACTIVITY.-h vitro testing against the murine leukemia P-388 (9PS)was conducted according to NCI procedures (1 1). In vitro cytotoxicity in NSCLCN6 was assayed by the following procedure: tests were conducted in 96-hole microplates (flat bottom microtest 111 plate with lid-Falcon 3072); 0.07 X IO5 cells were placed in each hole containing 50 ~1 of RPMI medium supplemented with 10% fetal bovine serum. The therapeutic solution to be tested (50 p.1)was added in decreasing concentration at the ratio of two holes for each dose. Microtest plates were incubated for 72 h at 37" in 5% CO, in air. The cell proliferation was estimated by colorimetric and immunological methods (12). Justicidin B showed the following activity: P-388 (9PS) ED,, 3.3 Fglml, NSCLCN6 IC,, 28 Fg/ml. ACKNOWLEDGMENTS The authors are grateful to D n . C. Moretti and M. Sauvain, ORSTOM Center of Cayenne, French Guyana, for supplying plant material.
600
Journal of Natural Products LITERATURE CITED
1.
2. 3. 4.
5. 6. 7.
8.
R.E. Schultes, Bot. Mus. Leap., H a w . Univ., 26,267 (1978). W. Wong, Eron. Bot., 30,103 (1976). J.F. Morton, Q.J . Cruale Drug Res., 15, 165 (1977). W. Donald Macrae and G.H. Neil Towers, J . Ethnopha-ol., 12,93 (1984). K. Munakata, S. Marumo, and K. Ohta, TetrahedronL.ett., 47, 4 167 (1965). M. Okigawa, T. Maeda, a n d N . Kawano, Tetrahedron, 26,4301 (1970). G.R. Pettit, M. Cragg, M.I. Suffness, D. Gust, F.E. Boettner, M. Williams, J.A. Saenz-Renauld, P. Brown, J.M. Schmidt, and P.D. Ellis, J . Org. Chem., 49, 4258 (1984). Y.H. Hui, C.-J. Chang, J.L. Mchughlin,
[Vol. 5 1, No. 3
and Richard G. Powell, J . Nat. Prod., 49, 1175 (1986). 9. C. Roussakis, G. Dabouis, C. Grata, and A. Audouin, in: “Abstracts of Papers,” v“ Symposium NCIEORTC, Amsterdam, October 22/24, 1986, Abstract 412. 10. J. Mensah, C. Moulis, J. Gleye, C. Moretti, and E. Stanislas, in: “Abstracts of Papers,” V“ CoIIoque International consacrk aux Plantes Medicinales et Substances d’Origine Naturelle, Angers 27-29 May, 1983, Abstract Al6. 11. R.I. Gem, N.H. Greenberg, M.M.Mac Donald, A.M. Schumacher, and B.J. Abbott, Cancer Chemother. Rep., 3(3), 1 (1972). 12. T. Mosmann, J . lmmunol. Methods, 65,5 5 (1983). Recciwd 13 November I987
