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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Docking and Pharmacokinetic Studies for Screening Terpenoids from Erythroxylum Species as Anticancer Agents

Author(s): Supriya A. Unavane*, Sabeena Syed, Hemant Kumar Jain and Amol Bansode

Volume 20, Issue 12, 2023

Published on: 25 October, 2022

Page: [2025 - 2033] Pages: 9

DOI: 10.2174/1570180819666220929121630

Price: $65

Abstract

Background: Cancer still remains a disease of concern with various side effects of synthetic chemotherapeutic agents. Hence, there is a continued need to develop safer therapies with fewer side effects. Erythroxylum species is a widely available source of various phytoconstituents, especially terpenoids.

Objective: To carry out the docking studies of a few terpenoids on validated targets like EGFR, VEGFR, CDK, and tubulin protein which are overexpressed in many types of cancers, and to estimate the pharmacokinetic and drug-likeness properties of these molecules using in silico techniques.

Materials: Protein structures were retrieved from Protein Data Bank, and the terpenoids were docked on each of the protein targets using Autodock 4.2. SwissADME was used to predict the pharmacokinetic and drug-likeness properties.

Results: Compounds show good binding affinity and inhibition constant for all targets except for tubulin, where few ligands could bind. They exhibit an excellent pharmacokinetic profile, and no significant violations in drug-likeness parameters were observed.

Conclusion: Compound 2 was found to be the most active agent against VEGFR, CDK, and tubulin, whereas compound 7 was most effective at EGFR. These compounds can be continued for further studies.

Keywords: Docking, Erythroxylum, Anticancer, Terpenoids, EGFR, VEGFR, CDK, Tubulin

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[1]
Plowman, T.; Hensold, N. Names, types, and distribution of neotropical species of Erythroxylum (Erythroxylaceae). Brittonia, 2004, 56(1), 1-53.
[http://dx.doi.org/10.1663/0007-196X(2004)056[0001:NTADON]2.0.CO;2]
[2]
Aguiar, J.S.; Araújo, R.O.; do Desterro Rodrigues, M.; Sena, K.X.F.R.; Batista, A.M.; Guerra, M.M.P.; Oliveira, S.L.; Tavares, J.F.; Silva, M.S.; Nascimento, S.C.; da Silva, T.G. Antimicrobial, antiproliferative and proapoptotic activities of extract, fractions and isolated compounds from the stem of Erythroxylum caatingae plowman. Int. J. Mol. Sci., 2012, 13(4), 4124-4140.
[http://dx.doi.org/10.3390/ijms13044124] [PMID: 22605969]
[3]
Li, L.S.; Chiroma, S.M.; Hashim, T.; Adam, S.K.; Mohd Moklas, M.A.; Yusuf, Z.; Rahman, S.A. Antioxidant and anti-inflammatory properties of Erythroxylum cuneatum alkaloid leaf extract. Heliyon, 2020, 6(6), e04141.
[http://dx.doi.org/10.1016/j.heliyon.2020.e04141] [PMID: 32637674]
[4]
Mayta-Tovalino, F.; Loyola, D.; Mendoza, R.; Chiong, L.; Rueda, M.; Alvítez-Temoche, D.; Gallo, W. Ethanol extract of Schinus molle L. (molle) and Erythroxylum coca Lam (coca): Antibacterial properties at different concentrations against Streptococcus mutans: An in vitro study. J. Int. Soc. Prev. Community Dent., 2020, 10(5), 579-584.
[http://dx.doi.org/10.4103/jispcd.JISPCD_237_20] [PMID: 33282766]
[5]
Manabe, H.; Sakagami, H.; Ishizone, H.; Kusano, H.; Fujimaki, M.; Wada, C.; Komatsu, N.; Nakashima, H.; Murakami, T.; Yamamoto, N. Effects of Catuaba extracts on microbial and HIV infection. In Vivo, 1992, 6(2), 161-165.
[PMID: 1525337]
[6]
Venkatesalu, V.; Gopalan, N.; Pillai, C.R.; Singh, V.; Chandrasekaran, M.; Senthilkumar, A.; Chandramouli, N. In vitro anti-plasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum. Parasitol. Res., 2012, 111(1), 497-501.
[http://dx.doi.org/10.1007/s00436-012-2834-9] [PMID: 22290450]
[7]
Barreiros, M.L.; David, J.P.; David, J.M.; Xavier Lopes, L.M.; de Sá, M.S.; Costa, J.F.O.; Almeida, M.Z.; de Queiróz, L.P.; Sant’Ana, A.E.G. Ryanodane diterpenes from two Erythroxylum species. Phytochemistry, 2007, 68(13), 1735-1739.
[http://dx.doi.org/10.1016/j.phytochem.2007.05.007] [PMID: 17570446]
[8]
Kauroo, S.; Govinden-Soulange, J.; Ranghoo-Sanmukhiya, V.M.; Miranda, K.; Cotham, W.E.; Walla, M.D.; Nagarkatti, M.; Nagarkatti, P. Extracts of select endemic plants from the Republic of Mauritius exhibiting anti-cancer and immunomodulatory properties. Sci. Rep., 2021, 11(1), 4272.
[http://dx.doi.org/10.1038/s41598-021-83461-0] [PMID: 33608608]
[9]
Ivelone, M De; Barros, C.; Bruno, H.M. Leite; Caio, F M Leite; Christopher, William, Fagg; Gomes, Sueli MARIA; Resck, Inês Sabioni; Fonseca, Yris; Magalhães, Pérola O Silveira, Damaris Chemical composition and antioxidant activity of extracts from Erythroxylum suberosum A.St. Hil.leaves. J. Appl. Pharm. Sci., 2017, 7(03), 88-94.
[10]
Ansell, S.M.; Pegel, K.H.; Taylor, D.A.H. Diterpenes from the timber of erythroxylum australe. Phytochemistry, 1993, 32(4), 937-943.
[http://dx.doi.org/10.1016/0031-9422(93)85233-H]
[11]
Connolly, J.D.; Harding, A.E. Constituents of erythroxylon species. Part VII. Diterpenoids from erythroxylon australe. J. Chem. Soc., Perkin Trans. 1, 1972, 1996-2000.
[http://dx.doi.org/10.1039/p19720001996]
[12]
Allen, T.M. Ligand-targeted therapeutics in anticancer therapy. Nat. Rev. Cancer, 2002, 2(10), 750-763.
[http://dx.doi.org/10.1038/nrc903] [PMID: 12360278]
[13]
Eastman, A.; Perez, R.P. New targets and challenges in the molecular therapeutics of cancer. Br. J. Clin. Pharmacol., 2006, 62(1), 5-14.
[http://dx.doi.org/10.1111/j.1365-2125.2006.02720.x] [PMID: 16842374]
[14]
Zhang, X.; Li, Y.; Li, H.; Qin, Y.; Bai, C.; Xu, F.; Zhu, T.; Xu, J.; Wu, M.; Wang, C.; Wei, L.; He, J. Combined EGFR and VEGFR versus single EGFR signaling pathways inhibition therapy for NSCLC: A systematic review and meta-analysis. PLoS One, 2012, 7(8), e40178.
[http://dx.doi.org/10.1371/journal.pone.0040178] [PMID: 22916093]
[15]
Veale, D.; Ashcroft, T.; Marsh, C.; Gibson, G.J.; Harris, A.L. Epidermal growth factor receptors in non-small cell lung cancer. Br. J. Cancer, 1987, 55(5), 513-516.
[http://dx.doi.org/10.1038/bjc.1987.104] [PMID: 3038157]
[16]
Uribe, M.L.; Marrocco, I.; Yarden, Y. EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance. Cancers (Basel), 2021, 13(11), 2748.
[http://dx.doi.org/10.3390/cancers13112748] [PMID: 34206026]
[17]
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[18]
Ding, L.; Cao, J.; Lin, W.; Chen, H.; Xiong, X.; Ao, H.; Yu, M.; Lin, J.; Cui, Q. The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. Int. J. Mol. Sci., 2020, 21(6), 1960.
[http://dx.doi.org/10.3390/ijms21061960] [PMID: 32183020]
[19]
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(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]

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