17-O-Acetyl,10-hydroxycorynantheol, a Selective Antiplasmodial Alkaloid Isolated from Strychnos usambarensis Leaves

Abstract

In the course of our investigations on Strychnos usambarensis leaves in order to isolate isostrychnopentamine, the main alkaloid responsible for the antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been isolated: 17-O-acetyl,10-hydroxycorynantheol 1. Its structure was determined by means of spectroscopic and spectrometric methods such as UV, IR, CD, NMR, and ESI-MS. 17-O-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric indole alkaloids known to date showing an in vitro activity against Plasmodium falciparum close to 5 µM and a high selectivity.

Key words

Strychnos usambarensis Gilg. - Loganiaceae - monomeric indole alkaloid - antiplasmodial - selectivity

References

• 1 Angenot L, Dubois M, Ginion C, van Dorsser W, Dresse A. Chemical structure and pharmacological (curarizing) properties of various indole alkaloids extracted from an African Strychnos.  Arch Int Pharmacodyn Ther. 1975;  215 246-258
• 2 Frederich M, Jacquier M J, Thepenier P, De Mol P, Tits M, Philippe G, Delaude C, Angenot L, Zeches-Hanrot M. Antiplasmodial activity of alkaloids from various Strychnos species.  J Nat Prod. 2002;  65 1381-1386
• 3 Bassleer R, Depauw-Gillet M C, Massart B, Marnette J M, Wiliquet P, Caprasse M, Angenot L. Effects of three alkaloids isolated from Strychnos usambarensis on cancer cells in culture.  Planta Med. 1982;  45 123-126
• 4 Tits M, Desaive C, Marnette J M, Bassleer R, Angenot L. Antimitotic activity of strychnopentamine, a bisindolic alkaloid.  J Ethnopharmacol. 1984;  12 287-292
• 5 Leclercq J, De Pauw-Gillet M C, Bassleer R, Angenot L. Screening of cytotoxic activities of Strychnos alkaloids (methods and results).  J Ethnopharmacol. 1986;  15 305-316
• 6 Bonjean K A, De Pauw-Gillet M C, Quetin-Leclercq J, Angenot L, Bassleer R J. In vitro cytotoxic activity of two potential anticancer drugs isolated from Strychnos: strychnopentamine and usambarensine.  Anticancer Res. 1996;  16 1129-1137
• 7 Frederich M, Tits M, Goffin E, Philippe G, Grellier P, De Mol P, Hayette M P, Angenot L. In vitro and in vivo antimalarial properties of isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis.  Planta Med. 2004;  70 520-525
• 8 Frederich M, Bentires-Alj M, Tits M, Angenot L, Greimers R, Gielen J, Bours V, Merville M P. Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, induces cell cycle arrest and apoptosis in human colon cancer cells.  J Pharmacol Exp Ther. 2003;  304 1103-1110
• 9 Saidou Balde el H, Megalizzi V, Cao M, Angenot L, Kiss R, Van Damme M, Frederich M. Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells.  Int J Oncol. 2010;  36 961-965
• 10 Angenot L, Coune C, Tits M. [New alkaloids from Strychnos usambarensis leaves (author's transl)].  J Pharm Belg. 1978;  33 11-23
• 11 Jork H, Funk W, Fisher W, Wimmer H. Thin-layer chromatography: reagents and detection methods. Weinheim, New York: VCH; 1994
• 12 Quetin-Leclercq J, Angenot L. 10-Hydroxy-Nb-methyl-corynantheol, a new quaternary alkaloid from the stem bark of Strychnos usambarensis.  Phytochemistry. 1988;  27 1923-1926
• 13 Trager W F, Lee C M, Beckett A H. Corynantheidine-type alkaloids: Establishment of physical criteria for the normal, pseudo, allo and epiallo configurations by conformational analysis.  Tetrahedron. 1966;  23 365-374
• 14 Zeches-Hanrot M, Sigaut F, Le Men-Olivier L, Lévy J, Le Men J. Alcaloïdes bis-indoliques monoterpénoïdes des feuilles du Cinchona ledgeriana Moens. Structure et hémisynthèse d'analogues structuraux.  Bull Soc Chim France. 1981;  II 75-79
• 15 Caprasse M, Tavernier D, Angenot L. Deux nouveaux alcaloïdes quaternaires isolés à partir des feuilles du Strychnos usambarensis du Rwanda: Nb-méthyl hydroxy-10 et hydroxy-11 usambarines.  J Pharm Belg. 1983;  38 211-218
• 16 Wenkert E, Bindra J S, Chang C J, Cochran D W, Schell F M. Carbon-13 nuclear magnetic resonance spectroscopy of naturally occurring substances. Alkaloids.  Accounts Chem Res. 1974;  7 46-51
• 17 Rottmann M, McNamara C, Yeung B K, Lee M C, Zou B, Russell B, Seitz P, Plouffe D M, Dharia N V, Tan J, Cohen S B, Spencer K R, Gonzalez-Paez G E, Lakshminarayana S B, Goh A, Suwanarusk R, Jegla T, Schmitt E K, Beck H P, Brun R, Nosten F, Renia L, Dartois V, Keller T H, Fidock D A, Winzeler E A, Diagana T T. Spiroindolones, a potent compound class for the treatment of malaria.  Science. 2010;  329 1175-1180
• 18 Frederich M, Hayette M P, Tits M, De Mol P, Angenot L. In vitro activities of Strychnos alkaloids and extracts against Plasmodium falciparum.  Antimicrob Agents Chemother. 1999;  43 2328-2331
• 19 Trager W, Jensen J B. Human malaria parasites in continuous culture.  Science. 1976;  193 673-675
• 20 Kenmogne M, Prost E, Harakat D, Jacquier M J, Frederich M, Sondengam L B, Zeches M, Waffo-Teguo P. Five labdane diterpenoids from the seeds of Aframomum zambesiacum.  Phytochemistry. 2006;  67 433-438
• 21 Jonville M C, Kodja H, Humeau L, Fournel J, De Mol P, Cao M, Angenot L, Frederich M. Screening of medicinal plants from Reunion Island for antimalarial and cytotoxic activity.  J Ethnopharmacol. 2008;  120 382-386
• 22 Stevigny C, Block S, De Pauw-Gillet M C, de Hoffmann E, Llabres G, Adjakidje V, Quetin-Leclercq J. Cytotoxic aporphine alkaloids from Cassytha filiformis.  Planta Med. 2002;  68 1042-1044