Antiplasmodial activity, in silico ADME and mammalian cell cytotoxicity of a synthetic protoberberine alkaloid, coralyne
Article Sidebar
Main Article Content
Abstract
Coralyne is a synthetic protoberberine alkaloid with anticancer activity and selectivity superior to that of berberine, its congener. As berberine is gifted with antiplasmodial activity, this study assessed the antiplasmodial activity of coralyne against erythrocytic stages of the malaria parasite in culture. Parasites were cultured by adopting the method described by Trager and Jensen in 1976. Following this, parasites were exposed at ring stage to increasing doses of coralyne to enable us compute the IC50. Further, given that berberine is a substrate of the efflux transporter permeability glycoprotein (P-gp), in silico techniques were used to study the pharmacokinetics of oral coralyne. Coralyne showed excellent potency (IC50Pf3D7: 0.52 µg/ml) against chloroquine sensitive strain and a little less potency (IC50PfINDO: 1.15 µg/ml) against the chloroquine resistant malaria parasite strain (Resistance index: 2.21). Further, with CC50HEK: >100 µg/ml, it was non-toxic to mammalian cells. However, in silico absorption, distribution, metabolism and excretion (ADME) studies predicts that like berberine, coralyne may also have poor oral bioavailability thus limiting its usefulness as an orally deliverable antimalarial agent. Given the negative impact of low bioavailability in the development of protoberberine alkaloids as antimalarials, synthesizing analogues of coralyne with nanomolar potency against the malaria parasite and improved oral pharmacokinetics may be a good strategy for the future.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Abookleesh, F.L, Al-Anzi, B.S. and Ullah A. (2022). Potential antiviral action of alkaloids. Molecules. 27: 903. doi:10.3390/molecules27030903
Ai, G., Huang, Z., Cheng, J., Xie, J., Zeng, H., Liu, Y., Li, Y., Huang, X., Chen, J. and Su, Z. (2021). Gut microbiota-mediated transformation of Coptisine into a novel metabolite 8-Oxocoptisine: Insight into its superior anti-colitis effect. Frontiers in Pharmacology. 12: 639020.
doi:10.3389/fphar.2021.639020
Al Azzam, K.M., Negim, E. and Aboul-Enein, H.Y. (2022). ADME studies of TUG-770 (a GRP-40 inhibitor agonist) for the treatment of type-2 diabetes using SwissADME predictor: In silico study. Journal of Applied Pharmaceutical Science. 12(4): 159-169
Bahar, M., Deng, Y., Zhu, X., He, S., Pandharkar, T., Drew, M.E., NavaroVázquez, A., Anklin, C., Gil, R.R., Doskotch, R.W., Werbovetz, K.A. and
Kinghorn, D. (2011). Potent antiplasmodial activity of a novel semi-synthetic berberine derivative. Bioorganic & Medicinal Chemistry Letters. 21: 2606-2610
Bapna, S., Choudhary, P.K., Ramalya, M. and Chowdhary, A. (2015). Antiplasmodial activity of Argemone mexicana: An in vivo in vitro study. World
Journal of Pharmaceutical Research. 4(11): 1653-1663
Belwar, T., Bisht, A., Devkota, H.P., Ullah, H., Khan, H., Pandey, A., Bhatt, I.D. and Echeverria, J. (2020). Phytopharmacology and clinical updates
of Berberis species against diabetes and other metabolic diseases. Frontiers in Pharmacology. 11: 2020. doi: 10.3389/fphar.2020.00041
Bourdat-Deschamps, M., Herrenknecht, C., Akendengue, B., Laurens, A. and Hocquemiller, R. (2004). Separation of protoberberine quaternary alkaloids from a crude extract of Enantia chlorantha by centrifugal partition chromatography. Journal of Chromatography A. 1041: 143–152
Din, N. (2011). Inventory and identification of plants used in the treatment of diabetes in Douala town (Cameroon). European Journal of Medicinal Plants. 1(3): 60-73 doi:10.9734/ejmp/2011/273
Erhunse, N., Kumari, S., Anmol, Singh, P., Omoregie, E.S., Singh, A.P., Sharma, U. and Sahal, D. (2024). Annickia affinis (Exell) Versteegh & Sosef methanol stem bark extract, potent fractions and isolated Berberine alkaloid target both blood and liver stages of malaria parasites. Journal
of Ethnopharmacology. 319 (2024): 117269.
Erhunse, N. and Okomayin, V. (2022). VectorParasite Interactions and Malaria Transmission. In: Puerta-Guardo, H., Manrique-Saide., P. (Eds.), Mosquito Research-Recent Advances in Pathogen Interactions, Immunity and Vector Control Strategies, IntechOpen, London, UK. pp 19-27. doi:
5772/intechopen.105025
Erhunse, N. and Sahal, D. (2022). Comparative Study on the Phytometabolites, in vitro Antiplasmodial Activity and Cytotoxicity of Stem Bark Extracts of Annickia affinis (Exell) Versteegh & Sosef and Annickia chlorantha (Oliv.) Setten & PJ. Mass. Nigerian Journal of Life Sciences. 12(2):
-21
Erhunse, N., Omoregie, E.S. and Sahal, D. (2023). Antiplasmodial and antimalarial evaluation of a Nigerian hepta-herbal Agbo-iba decoction: Identification of magic bullets and possible facilitators of drug action. Journal of Ethnopharmacology. 301: 115807. doi: 10.1016/j.jep.2022.115807
Filli, M.S., Ibrahim, A.A., Kesse, S., Aquib, M., Boakye-Yiadom, K.O., Farooq, M.A., Raza, F., Zhang Y and Wang B. (2022). Synthetic berberine derivatives as potential new drugs. Brazilian Journal of Pharmaceutical Sciences. 58: e18835
Hsieh, T.J., Chia, Y.C., Wu, Y.C. and Chen, C.Y. (2004). Chemical constituents from the stems of Mahonia japonica. Journal of the Chinese Chemical
Society, 51(2): 443-446. doi:10.1002/jccs.200400068
Imenshahidi, M. and Hosseinzadeh, H. (2016). Berberis Vulgaris and Berberine: An Update Review. Phytotherapy Research. 30(11):1745-1764. doi: 10.1002/ptr.5693
Imieje, V., Zaki, A.A., Fasinu, P.S., Ali, Z., Khan, I.A., Tekwani, B., Khan, S.I., Nosa, E.O. and Falodun, A. (2017). Antiprotozoal and cytotoxicity studies of fractions and compounds from Enantia chlorantha. Tropical Journal of Natural Product Research. 1(2): 89-94. doi:10.26538/tjnpr/v1i2.8.
Lambros, C. and Vanderberg, J.P. (1979). Synchronization of Plasmodium falciparum erythrocytic stages in culture. Journal of Parasitology. 65 (3): 418-420
Liu, Y., Hao, H., Xie, H., Lai, L., Wang, Q., Liu, C. and Wang, G. (2010). Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metabolism & Disposition. 38(10): 1779-1784
Ma, C., Harrison, P., Wang, L. and Coppel, R.L. (2010). Automated estimation of parasitaemia of Plasmodium yoeliiinfected mice by digital image analysis of Giemsa-stained thin blood smears. Malaria Journal. 9: 348. doi:10.1186/1475-2875-9-348
Maeng, H.J., Yoo, H.J., Kim, I.W., Song, I.S., Chung, S.J. and Shim, C.K. (2002). Pglycoprotein-mediated transport of berberine across Caco-2 cell
monolayers. Journal of Pharmaceutical Sciences. 91(12): 2614-2621. doi:10.1002/jps.10268
Maiti, M. and Kumar, G.S. (2010). Polymorphic nucleic acid binding of bioactive isoquinoline alkaloids and their role in cancer. Journal of Nucleic Acids. 2010: 1–23. doi:10.4061/2010/593408.
Megyesi, M. and Biczok, L. (2010). Considerable change of fluorescence properties upon multiple binding of coralyne to 4-sulfonatocalixarenes.
The Journal of Physical Chemistry B. 114: 2814 - 2819
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal
of Immunological Methods. 16: 55-63 doi: 10.1016/0022-1759(83)90303-4
Nzila, A. and Mwai, L. (2010). In vitro selection of Plasmodium falciparum drug-resistant parasite lines. The Journal of Antimicrobial Chemotherapy. 65: 390-398
Ogihara, T., Kamiya, M., Ozawa, M., Fujita, T., Yamamoto, A., Yamashita, S., Ohnishi, S. and Isomura, Y. (2006). What kind of substrates show P-glycoproteindependent intestinal absorption? Comparison of verapamil with vinblastine. Drug Metabolism & Pharmacokinetics. 21(3): 238-244
Pal, S., Das, S., Suresh, G. and Maiti, M. (1998). Antitumor agent coralyne: A guanine-cytosine specific DNA-binding alkaloid. Current Science. 75(5): 496-500
Pan, G.Y., Wang, G.J., Liu, X.D., Fawcett, J.P. and Xie, Y.Y. (2002). The involvement of P-glycoprotein in berberine absorption. Pharmacology & Toxicology. 91: 193–197
Phillipson, J.D. and Wright, C.W. (1991). Antiprotozoal agents from plant sources. Planta Medica. 57(7): 53-59. doi:10.1055/s-2006-960230
Prudêncio, M., Rodriguez, A. and Mota, M.M. (2006). The silent path to thousands of merozoites: The Plasmodium liver stage. Nature Reviews Microbiology. 4: 849-856
Silikas, N., Mccall, D.L.C., Sharples, D., Watkins, W.M., Waigh, R.D. and Barber, J. (1996). The antimalarial activity of berberine and some synthetic
analogues. Pharmacy & Pharmacology Communications. 2(1): 55-58
Simoes-Pires,C., Hostettmann,K., Haouala,A., Cuendet, M., Falquet, J., Graz, B. and Christen, P. (2014). Reverse pharmacology for developing an antimalarial phytomedicine. The example of Argemone mexicana. International Journal for Parasitology: Drugs & Drug Resistance. 4: 338–346.
Smilkstein, M., Sriwilaijaroen, N., Kelly, J.X., Wilairat, P. and Riscoe, M. (2004). Simple and Inexpensive FluorescenceBased Technique for High-Throughput Antimalarial Drug Screening. Antimicrobial Agents & Chemotherapy. 48: 1803–1806. doi: 10.1128/AAC.48.5.1803-1806.2004
Tan, X.S., Ma, J.Y., Feng, R., Ma, C., Chen, W.J., Sun, Y.P., Fu, J., Huang, M., He, C.Y., Shou, J.W., He, W.Y., Wang, Y. and Jiang, J.D. (2013). Tissue
distribution of berberine and its metabolites after oral administration in rats. PLoS One. 8: 1–9. doi: 10.1371/journal.pone.0077969
Tarabasz, D. and Kukula‐Koch, W. (2020). Palmatine: A review of pharmacological properties and pharmacokinetics. Phytotherapy Research. 34: 33–50. doi: 10.1002/ptr.6504
Tillhon, M., Guamán, O.L.M., Lombardi, P. and Scovassi, A.I. (2012). Berberine: New perspectives for old remedies. Biochemical Pharmacology. 84: 1260–1267. doi: 10.1016/j.bcp.2012.07.018
Trager, W. and Jensen, J.B. (1976). Human malaria parasites in continuous culture. Science. 193: 673–675. doi: 10.1126/science.781840
Tripathi, P., Ghosh, S. and Talapatra, N. (2019). Bioavailability prediction of phytochemicals present in Calotropis procera (Aiton) R. Br. By using SwissADME tool. World Scientific News. 131: 147-163
Tsai, P.L. and Tsai, T.H. (2004). Hepatobiliary excretion of berberine. Drug Metabolism & Disposition. 32: 405–412
Vennerstrom, J.L. and Klayman, D.L. (1988). Protoberberine Alkaloids as Antimalarials. Journal of Medicinal Chemistry. 31(6): 1084-1087. doi:
1021/jm00401a006
Wang, Y., Feng, R., Shou, J., Zhao, Z. and Jiang, J. (2015). “Transforming Berberine into its intestine-absorbable form by the gut microbiota.” Scientific Reports. 5: 1–15. doi:10.1038/srep12155
Węgierek-Ciuk, A., Arabski, M., Ciepluch, K., Brzóska, K., Lisowska, H., Czerwińska, M., Stępkowski, T., Lis, K. and Lankoff, A. (2021). Coralyne radiosensitizes A549 cells by upregulation of CDKN1A expression to attenuate radiation induced G2/M block of the cell cycle. International Journal of Molecular Sciences. 22(11): 5791. doi: 10.3390/ijms22115791
Wright, C.W., Marshall, S.J., Russell, P.F., Anderson, M.M., Phillipson, J.D., Kirby, G.C., Warhurs, D.C. and Schiff, J.L. (2000). In vitro antiplasmodial,
antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids. Journal of Natural Products. 63:1638–1640.
doi:10.1021/np000144r
Zhou, J., Sayre, D.A., Zheng, Y., Szmacinski, H. and Sintim, H.O. (2014). Unexpected complex formation between Coralyne and cyclic diadenosine monophosphate providing a simple fluorescent turn-on assay to detect this bacterial second messenger. Analytical Chemistry. 86(5): 2412–2420
Zou, K., Li, Z., Zhang, Y., Zhang, H.Y., Li, B., Zhu, W.L., Shi, J.Y., Jia, Q. and Li, Y.M. (2017). Advances in the study of berberine and its derivatives: A focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacologica Sinica. 38: 157–167. doi: 10.1038/aps.2016.125