[en] Strychnogucine B is a bisindole alkaloid previously isolated from Strychnos icaja that possesses promising in vitro antiplasmodial properties. This compound was synthesized in four steps from (−)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its in vivo antimalarial activity was determined intraperitoneally at 30mg/kg/d in a Plasmodium berghei murine model. In the Petersʼs 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activity but no in vivo activity in an acute Trypanosoma brucei model. It was also inactive in vitro on Leishmania mexicana promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Beaufays, Claire ✱
Ledoux, Allison ✱; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Jansen, Olivia ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
bordignon, Annélise
Zhao, Senzhi
Teijaro, Christiana
Andrade, Rodrigo
Quetin-Leclercq, Joëlle
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
✱ These authors have contributed equally to this work.
Language :
English
Title :
In vivo antimalarial and antitrypanosomal activity of strychnogucine B, a bisindole alkaloid from Strychnos icaja.
Koehn, F.E., Carter, G.T., The evolving role of natural products in drug discovery (2005) Nat Rev Drug Discov, 4, pp. 206-220
Bero, J., Frédérich, M., Quetin-Leclercq, J., Antimalarial compounds isolated from plants used in traditional medicine (2009) J Pharm Pharmacol, 61, pp. 1401-1433
Jampilek, J., Design of antimalarial agents based on natural products (2017) Curr Org Chem, 21, pp. 1824-1846
Memvanga, P.B., Tona, G.L., Mesia, G.K., Lusakibanza, M.M., Cimanga, R.K., Antimalarial activity of medicinal plants from the Democratic Republic of Congo: A review (2015) J Ethnopharmacol, 169, pp. 76-98
Frederich, M., Hayette, M.P., Tits, M., De Mol, P., Angenot, L., In vitro activities of Strychnos alkaloids and extracts against Plasmodium falciparum (1999) Antimicrob Agents Chemother, 43, pp. 2328-2331
Frédérich, M., Jacquier, M.J., Thépenier, P., De Mol, P., Tits, M., Philippe, G., Delaude, C., Zèches-Hanrot, M., Antiplasmodial activity of alkaloids from various Strychnos species (2002) J Nat Prod, 65, pp. 1381-1386
Frédérich, M., De Pauw, M.C., Prosperi, C., Tits, M., Brandt, V., Penelle, J., Hayette, M.P., Angenot, L., Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja (2001) J Nat Prod, 64, pp. 12-16
Philippe, G., De Mol, P., Angenot, L., Tits, M., Frédérich, M., In vivo antimalarial activity of isosungucine, an indolomonoterpenic alkaloid from Strychnos icaja (2007) Planta Med, 73, pp. 478-479
Philippe, G., Nguyen, L., Angenot, L., Frédérich, M., Moonen, G., Tits, M., Rigo, J.M., Study of the interaction of antiplasmodial strychnine derivatives with the glycine receptor (2006) Eur J Pharmacol, 530, pp. 15-22
Zhao, S., Teijaro, C.N., Chen, H., Sirasani, G., Vaddypally, S., Zdilla, M.J., Dobereiner, G.E., Andrade, R.B., Concise syntheses of bis- Strychnos alkaloids (-)-sungucine, (-)-isosungucine, and (-)-strychnogucine B from (-)-strychnine (2016) Chem Weinh Bergstr Ger, 22, pp. 11593-11596
Ioset, J.R., Brun, R., Wenzler, T., Kaiser, M., Yardley, V., (2009) Drug Screening for Kinetoplastids Diseases: A Training Manual for Screening in Neglected Diseases, , https://www.dndi.org/2009/media-centre/scientific-articles/scientific-articles-hat/drug-screening-for-kinetoplastid-diseases-a-training-manual-for-screening-in-neglected-diseases/, Accessed June 20, 2018
Peters, W., Robinson, B.L., The chemotherapy of rodent malaria. XLVI. Reversal of mefloquine resistance in rodent Plasmodium (1991) Ann Trop Med Parasitol, 85, pp. 5-10
Pink, R., Hudson, A., Mouriès, M.A., Bendig, M., Opportunities and challenges in antiparasitic drug discovery (2005) Nat Rev Drug Discov, 4, pp. 727-740
Tchinda, A.T., Jansen, O., Nyemb, J.N., Tits, M., Dive, G., Angenot, L., Frédérich, M., Strychnobaillonine, an unsymmetrical bisindole alkaloid with an unprecedented skeleton from Strychnos icaja roots (2014) J Nat Prod, 77, pp. 1078-1082
Tchinda, A.T., Ngono, A.R., Tamze, V., Jonville, M.C., Cao, M., Angenot, L., Frédérich, M., Antiplasmodial alkaloids from the stem bark of Strychnos malacoclados (2012) Planta Med, 78, pp. 377-382
Frederich, M., Tits, M., Angenot, L., Potential antimalarial activity of indole alkaloids (2008) Trans R Soc Trop Med Hyg, 102, pp. 11-19
Girardot, M., Deregnaucourt, C., Deville, A., Dubost, L., Joyeau, R., Allorge, L., Rasoanaivo, P., Mambu, L., Indole alkaloids from Muntafara sessilifolia with antiplasmodial and cytotoxic activities (2012) Phytochemistry, 73, pp. 65-73
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 (2004) Planta Med, 70, pp. 520-525
Wright, C.W., Bray, D.H., O'Neill, M.J., Warhurst, D.C., Phillipson, J.D., Quetin-Leclercq, J., Angenot, L., Antiamoebic and antiplasmodial activities of alkaloids isolated from Strychnos usambarensis (1991) Planta Med, 57, pp. 337-340
Ramanitrahasimbola, D., Rasoanaivo, P., Ratsimamanga-Urverg, S., Federici, E., Palazzino, G., Galeffi, C., Nicoletti, M., Biological activities of the plant-derived bisindole voacamine with reference to malaria (2001) Phytother Res, 15, pp. 30-33
Pollitt, L.C., Macgregor, P., Matthews, K., Reece, S.E., Malaria and trypanosome transmission: Different parasites, same rules? (2011) Trends Parasitol, 27, pp. 197-203
Babokhov, P., Sanyaolu, A.O., Oyibo, W.A., Fagbenro-Beyioku, A.F., Iriemenam, N.C., A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis (2013) Pathog Glob Health, 107, pp. 242-252
Da Silva Oliveira, G.L., De Freitas, R.M., Diminazene aceturate - An antiparasitic drug of antiquity: Advances in pharmacology & therapeutics (2015) Pharmacol Res, 102, pp. 138-157
Hoet, S., Opperdoes, F., Brun, R., Adjakidjé, V., Quetin-Leclercq, J., In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants (2004) J Ethnopharmacol, 91, pp. 37-42
Hoet, S., Pieters, L., Muccioli, G.G., Habib-Jiwan, J.L., Opperdoes, F.R., Quetin-Leclercq, J., Antitrypanosomal activity of triterpenoids and sterols from the leaves of Strychnos spinosa and related compounds (2007) J Nat Prod, 70, pp. 1360-1363
Pan, L., Terrazas, C., Muñoz Acuña, U., Ninh, T.N., Chai, H., Carcache De Blanco, E.J., Soejarto, D.D., Kinghorn, A.D., Bioactive indole alkaloids isolated from Alstonia angustifolia (2014) Phytochem Lett, 10, pp. 54-59
Ogungbe, I.V., Ng, J.D., Setzer, W.N., Interactions of antiparasitic alkaloids with Leishmania protein targets: A molecular docking analysis (2013) Future Med Chem, 5, pp. 1777-1799
Lage, P.S., De Andrade, P.H., Lopes Ade, S., Chávez Fumagalli, M.A., Valadares, D.G., Duarte, M.C., Pagliara Lage, D., Coelho, E.A., Strychnos pseudoquina and its purified compounds present an effective in vitro antileishmanial activity (2013) Evid Based Complement Altern Med, 2013, p. 304354
Beaufay, C., Hérent, M.F., Quetin-Leclercq, J., Bero, J., In vivo anti-malarial activity and toxicity studies of triterpenic esters isolated form Keetia leucantha and crude extracts (2017) Malar J, 16, p. 406
Jansen, O., Tits, M., Angenot, L., Nicolas, J.P., De Mol, P., Nikiema, J.B., Frédérich, M., Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound (2012) Malar J, 11, p. 289
Fidock, D.A., Rosenthal, P.J., Croft, S.L., Brun, R., Nwaka, S., Antimalarial drug discovery: Efficacy models for compound screening (2004) Nat Rev Drug Discov, 3, pp. 509-520
Bero, J., Hannaert, V., Chataigné, G., Hérent, M.F., Quetin-Leclercq, J., In vitro antitrypanosomal and antileishmanial activity of plants used in Benin in traditional medicine and bio-guided fractionation of the most active extract (2011) J Ethnopharmacol, 137, pp. 998-1002
Bero, J., Ganfon, H., Jonville, M.C., Frédérich, M., Gbaguidi, F., Demol, P., Moudachirou, M., Quetin-Leclercq, J., In vitro antiplasmodial activity of plants used in Benin in traditional medicine to treat malaria (2009) J Ethnopharmacol, 122, pp. 439-444
Herbert, W.J., Lumsden, W.H., Trypanosoma brucei: A rapid matching method for estimating the host's parasitemia (1976) Exp Parasitol, 40, pp. 427-431