New Antimalarial and Cytotoxic Sungucine Derivatives from Strychnos icaja Roots

Abstract

Reinvestigation of Strychnos icaja Baillon resulted in the isolation of vomicine, isostrychnine and of three new sungucine derivatives, named isosungucine (8), 18-hydroxy-sungucine (9) and 18-hydroxy-isosungucine (10). They were identified by detailed spectroscopic methods. The complete ¹H- and ¹³C-NMR study of sungucine was also realized. Some of these compounds were highly active against Plasmodium falciparum in vitro and more particularly against the chloroquine-resistant strain. Compound 10 showed a selective antiplasmodial activity, with > 100-fold greater toxicity towards Plasmodium falciparum, relative to cultured human cancer cells (KB and HeLa lines) or fibroblasts (WI38).

Sungucine - isostrychnine - vomicine - Strychnos icaja - Loganiaceae - antimalarial activity - cytotoxicity - Plasmodium falciparum

References

• 1 Neuwinger  H D.. African Ethnobotany, Poisons and Drugs, Chemistry-Pharmacology-Toxicology. Chapman & Hall, London; 1996: 569-78
• 2 Sandberg  F,, Roos  K,, Ryrberg  K J,, Kristianson  K.. A new alkaloid, 4-hydroxystrychnine, from african species Strychnos icaja Baill.  Tetrahedron Letters. 1968;;  59 6217-8
• 3 Kambu  K,, Coune  C,, Angenot  L.. Nouveaux alcaloïdes des racines du Strychnos icaja.  Planta Med.. 1979;;  37 161-4
• 4 Wright  C W,, Allen  D,, Cai  Y,, Zhenping  C,, Phillipson  D,, Kirby  G C, et al.. Selective antiprotozoal activity of some Strychnos alkaloids.  Phytother. Res.. 1994;;  8 149-52
• 5 Frédérich  M,, Tits  M,, Hayette  M P,, Brandt  V,, Penelle  J,, De Mol  P, et al.. 10′-Hydroxyusambarensine, a new antimalarial bisindole alkaloid from the roots of Strychnos usambarensis.  J. Nat. Prod.. 1999;;  62 619-21
• 6 Saxton  J E.. Indoles, part four, The Monoterpenoid Indole Alkaloids. Wiley and Sons, New York; 1983:: 320-4
• 7 Bisset  N G,, Das  B C,, Parello  J.. Alkaloids from the leaves of Strychnos icaja Baill.  Tetrahedron. 1973;;  29 4137-48
• 8 Bisset  N G,, Khalil  A.. New alklaoids from Strychnos icaja.  Phytochemistry. 1976;;  15 1973-6
• 9 Galeffi  C,, Delle Monache  E M,, Marini-Bettolo  G B.. Strychnos alkaloids. XXVII. Separation and characterisation of isostrychnine in Strychnos nux vomica L. seeds.  J. Chromatogr.. 1974;;  88 416-8
• 10 Verpoorte  R,, Hylands  P J,, Bisset  N G.. Carbon-13 NMR spectroscopy of some Strychnos alkaloids.  Org. Magn. Res.. 1977;;  9 567-71
• 11 Trager  W., Jensen  J B.. Human malaria parasites in continuous cultures.  Science. 1976;;  193 673-5
• 12 Desjardins  R,, Canfield  C,, Haynes  J D,, Chulay  J.. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.  Antimicrob. Agents Chemother.. 1979;;  16 710-8
• 13 Mirovsky  P,, Gay  F,, Bustos  D,, Mazier  D,, Gentilini  M.. Cloning of a fresh isolate of Plasmodium flaciparum and drug sensitivity of the clones.  Trans. Roy. Soc. Trop. Med. Hyg.. 1990;;  84 511-5
• 14 Bonjean  K,, De Pauw  M C,, Quetin-Leclerq  J,, Angenot  L,, Bassleer  R.. In vitro cytotoxic activity of two potential anticancer drugs isolated from Strychnos: strychnopentamine and usambarensine.  Anticancer Res.. 1996;;  16 1129-38
• 15 Verpoorte  R.. Assignment of ¹³C-NMR spectra of strychnine and brucine.  J. Pharm. Science. 1980;;  69 865-67
• 16 Lounasmaa  M,, Tolvanen  A.. ¹H-NMR data of monoterpenoid alkaloid.  Heterocycles. 1986;;  24 3229-81
• 17 Lamotte  J,, Dupont  L,, Dideberg  O,, Kambu  K,, Angenot  L.. Isolation and structure of sungucine: a new type of bisindoline alkaloid.  Tetrahedron Letters. 1979;;  43 4227-8
• 18 Dupont  L,, Dideberg  O,, Lamotte  J,, Kambu  K,, Angenot  L.. Structure d'un nouvel alcaloïde bisindolinique: Complexe moléculaire 1 : 1 Sungucine - Acétone.  Act. Crystallogr.. 1980;;  36 1672-5
• 19 Klyne  W,, Buckingham  J.. Atlas of Stereochemistry - Absolute Configurations of Organic Molecules. Chapman and Hall, London; 1974: 150-1
• 20 Massiot  G,, Massoussa  B,, Jacquier  M,, Thépenier  P,, Le-Men-Olivier  L,, Delaude  C,, Verpoorte  R.. Alkaloids from roots of Strychnos matopensis.  Phytochemistry. 1988;;  27 3293-3304
• 21 Wenkert  E,, Cheung  A,, Gottlieb  H,, Koch  M,, Rabaron  A,, Plat  M.. Carbon 13 NMR spectroscopy of naturally occurring substances.  J. Org. Chem.. 1978;;  43 1099-105
• 22 Tavernier  D,, Anteunis  M,, Tits  M,, Angenot  L.. The ¹H-NMR spectra of the strychnos alkaloids retuline, isoretuline and their N-deacetyl compounds.  Bull. Soc. Chim. Belg.. 1978;;  87 595-607
• 23 Gadi Biala  R,, Tits  M,, Penelle  J,, Frédérich  M,, Brandt  V,, Prospéri  C, et al.. Strychnochrysine, a new bisindole alkaloid from the roots of Strychnos nux-vomica.  J. Nat. Prod.. 1998;;  61 139-41
• 24 Phillipson  J,, Zenk  M.. Indole and related alkaloids. Academic Press Editions, London; 1980: 52-6