Vepris nobilis plant: a potential source of anticancer agents

Carolyne Chepkirui, Richard Kagia


Background: Cancer is one of the major causes of death worldwide. Current cancer therapy is costly, it has poor therapeutic outcomes and many side effects. Therefore, new medications are needed. Plants have been used as sources of anticancer drugs. Vepris species have anticancer properties. The purpose of this study is to assess Vepris nobilis, a plant found in Kenya as a potential source of anticancer drugs.

Methods: The dichloromethane/methanol (CH2Cl2/MeOH) 1:1 extract of the stem bark of Vepris nobilis led to the isolation of an alkaloid named, 4,6-dimethoxy-7-((3-methylbuta-1,3-dien-1-yl)oxy)furo[2,3-b]quinolone. SwissADME online tool was used to assess the compound’s pharmacokinetic parameters. Pass online tool identified potential targets while protox server described the toxicity of the compound. Chimera and Avogadro softwares were used for molecular docking studies.

Results: In-silico pharmacokinetic studies, showed that the isolated compound complied with Lipinski rule of five, it showed high gastrointestinal activity, and it also inhibits cytochrome P450 (CYP) isoforms 1A2, 2C9 and 2C19. In toxicity studies the compound was relatively safe with a predicted median lethal dose (LD50) of 1600 mg/kg, apart from potential immunotoxicity and mutagenicity. Molecular docking studies demonstrated that, the compound has potential anticancer activity, it interacted with deoxyribonucleic acid (DNA) topoisomerase I in an almost similar manner to camptothecin though it had less binding potential.

Conclusions: 4,6-dimethoxy-7-((3-methylbuta-1,3-dien-1-yl)oxy) furo[2,3-b]quinolone derived from Vepris nobilis is a potential drug for the management of cancer which can be administered orally.


Cancer, In-silico, Molecular docking, Pharmacokinetic, Vepris nobilis

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Adem FA. Phytochemical analysis of selected plants in the leguminosae and moraceae families for anticancer principles. University Nairobi. 2019;315.

Parkin A, Man J, Timpson P, Pajic M. Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy. FEBS J. 2019;286:3510-39.

Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, et al. A broad-spectrum integrative design for cancer prevention and therapy. Semin Cancer Biol. 2015;35:276.

Seebacher NA, Stacy AE, Porter GM, Merlot AM. Clinical development of targeted and immune based anti-cancer therapies. J Exp Clin Cancer Res. 2019;38:156.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018;68:394-424.

Zarocostas J. Global cancer cases and deaths are set to rise by 70% in next 20 years. Br Med J Online. 2010;340.

Topazian H, Cira M, Dawsey SM, Kibachio J, Kocholla L, Wangai M, Welch J, et al. Joining forces to overcome cancer: The Kenya cancer research and control stakeholder program. J. Cancer Policy. 2016;7:36-41.

Siddiqui M, Rajkumar SV. The high cost of cancer drugs and what we can do about it. Mayo Clin Proc. 2012;87:935-43.

Faden RR, Chalkidou K, Appleby J, Waters HR, Leider JP. Expensive cancer drugs: a comparison between the United States and the United Kingdom. Milbank Q. 2009;87:789-819.

Lichtenberg FR. How cost-effective are new cancer drugs in the U.S.? Expert Rev Pharmacoecon Outcomes Res. 2020;1-17.

Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141:69-80.

Wilson C, Nicholes K, Bustos D, Lin E, Song Q, Stephan JP, et al. Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition. Oncotarget. 2014;5:7328-41.

Brown R, Links M. Clinical relevance of the molecular mechanisms of resistance to anti-cancer drugs. Expert Rev Mol Med. 1999;1:1-21.

Nurgali K, Jagoe RT, Abalo R. Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? Front Pharmacol. 2018;9:245.

Thomas CJ, Rahier NJ, Hecht SM. Camptothecin: current perspectives. Bioorg Med Chem. 2004;12:1585-604.

Kumar A, Patil D, Rajamohanan PR, Ahmad A. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS one. 2013;8.

Islam KJJ, Koorbanally NA. A novel flavonoid and furoquinoline alkaloids from Vepris glomerata and their antioxidant activity. Nat Prod Commun. 2011;6.

Chaturvedula PVS, Schilling JK, Miller JS, Andriantsiferana R, Rasamison VE, Kingston DGI. New cytotoxic alkaloids from the wood of vepris punctata from the Madagascar rainforest. J Nat Prod. 2003;66:532-4.

Maggi F, Randriana FR, Rasoanaivo P, Nicoletti M, Quassinti L, Bramucci M, et al. Chemical composition and in vitro biological activities of the essential oil of Vepris macrophylla (Baker) I.Verd. Endemic to Madagascar. Chem Biodivers. 2013;10:356-66.

Imbenzi PS, Osoro EK, Aboud NS, Omollo J, Cheplogoi PK. A review on chemistry of some species of genus Vepris (Rutaceae family). 2014;3(3):357-62.

Geldenhuys WJ, Gaasch KE, Watson M, Allen DD, Van der Schyf CJ. Optimizing the use of open-source software applications in drug discovery. Drug Discov Today. 2006;11:127-32.

Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol. 2007;152:9-20.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717.

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46:257-63.

Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, Pogodin PV, Poroikov VV. Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chem Heterocycl Comp. 2014;50:444-57.

Hanwell MD, Curtis DE, Lonie DC, Vandermeerschd T, Zurek, E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminformatics. 2012;4:4-17.

Yang Z, Lasker K, Schneidman-Duhovny D, Webb B, Huang CC, Pettersen EF, Goddard TD, Meng EC, et al. UCSF Chimera, MODELLER, and IMP: An integrated modeling system. J Struct Biol. 2012;179:269-78.

Ayafor JF, Okogun JI. Nkolbisine, a New Furoquinoline Alkaloid, and 7-Deacetylazadirone From Teclea verdoorniana. Available at: Accessed on: 26 May 2020.

Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem. 2010;53:2719-40.

Capuzzi SJ, Muratov EN, Tropsha A. Phantom PAINS: Problems with the Utility of Alerts for Pan-Assay in terference Compound S. J Chem Inf Model. 2017;57:417-27.

Lipinski CA. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol. 2004;1:337-41.

Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45:2615-23.

Faber MS, Jetter A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97:125-34.

Rettie AE, Jones JP. Clinical and toxicological relevance of CYP2C9: Drug-Drug Interactions and Pharmacogenetics. Annu Rev Pharmacol Toxicol. 2005;45:477-94.

Wedlund PJ. The CYP2C19 enzyme polymorphism. Pharmacol. 2000;61:174-83.

Seino Y, Nagao M, Yahagi T, Hoshi A, Kawachi T, Sugimura T. Mutagenicity of several classes of antitumor agents to Salmonella typhimurium TA98, TA100, and TA92. Cancer Res. 1978;38:2148-56.

Wang X, Zhou X, Hecht SM. Role of the 20-hydroxyl group in camptothecin binding by the topoisomerase I-DNA binary complex. Biochem. 1999;38:4374-81.

Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006;6:789-802.