Pharmacokinetic properties and potential inhibition of tyrosine kinase of phenolic caffeates

Bruno Pereira Gabriel, Mayara Fernanda Strada, Rafaelle Bonzanini Romero, Adriano Lopes Romero


According to the National Cancer Institute, 582.590 new cases of cancer were registered in Brazil in 2018, constituting a public health problem. This picture progressively stimulates research and development (R&D) of new antineoplastic agents. However, the R&D process is disrupted and costly when carried out by application methods, so the in silico approach is shown as a viable alternative to these methodologies, making it less expensive and collapsed. In this perspective, the objective of this work was to develop an in silico study aiming to evaluate the pharmacokinetic properties and the potential of tyrosine kinase inhibition of phenolic derivatives of caffeic acid, which are the natural products that are highlighted by their therapeutic potential. According to the results obtained, the compounds used for analysis of the molecular and pharmacokinetic properties of drug candidates. The molecular anchorage study showed that caffeic acid phenol, p-salicildehyde and carvacrol interacted in active site of tyrosine kinase with energy, in kcal.mol-1, of -99.20, -88.07 and -99.90, respectively. By considering, the three phenolic caffeates indicated have potential for tyrosine kinase inhibition and are candidates for antineoplastic agents.


In silico study; Caffeic acid hybrids; Enzymatic Inhibition.


Ani, V., Varadaraj, M.C. & Naidu, K.A. (2006). Antioxidant and antibacterial activities of polyphenolic compounds from bitter cumin (Cuminum nigrum L.). European Food Research and Technology, 224(1):109-115.

Avila, C.M. & Romeiro, N.C. (2010). Proteínas tirosinas quinases: desafios do desenvolvimento de fármacos para a terapia do câncer. Revista Virtual de Química, 2(1):59-82.

Carvalheiro, J.R. (2002). O crucial debate da ciência no limiar do século 21. Ciência Saúde Coletiva, 7(1):17-41.

Chen, Y.F., Tsai, H. & Wu, T.S. (1995). Anti-inflammatory and analgesic activities from roots of Angelica pubescens. Planta medica, 61(01):2-8.

Huang, W.Y., Cai, Y.Z. & Zhang, Y. (2009). Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutrition and Cancer, 62(1):1-20.

Kang, N.J., Lee, K.W., Shin, B.J., Jung, S.K., Hwang, M.K., Bode, A.M., Heo, Y.S., Lee, H.J. & Dong, Z. (2009). Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVB-induced COX-2 expression. Carcinogenesis, 30(2):321-330.

Kauark, F., Manhães, F.C. & Medeiros, C.H. (2010). Metodologia da pesquisa: guia prático. Itabuna: Via Litterarum.

Lin, J.H. & Yamazaki, M. (2003). Role of P-glycoprotein in pharmacokinetics. Clinical Pharmacokinetics, 42(1):59-98.

Lipinski, C.A., Lombardo, F., Dominy, B.W. & Feeney, P.J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1-3):3-25.

Marcondes, D.L.Z., Romero, R.B. & Romero, A.L. (2018, maio). Estudos in silico de derivados de ácido cafeico como inibidores de monoamina oxidase. Anais do Congresso Científico da Região Centro Ocidental do Paraná, Campo Mourão, Paraná, Brasil, 2018, 9.

Chandra Mohan, A., Geetha, S., Gajalakshmi, R., Divya, S.R. & Dhanarajan, M.S. (2017). Determination of molecular property, bioactivity score and binding energy of the phytochemical compounds present in Cassia auriculata by Molinspiration and DFT method. Texila International Journal of Basic Medical Science, 2(2):1-15.

Olthof, M.R., Hollman, P.C. & Katan, M.B. (2001). Chlorogenic acid and caffeic acid are absorbed in humans. The Journal of Nutrition, 131(1):66-71.

Overington, J. P, Al-Lazikani, B. & Hopkins, A.L. (2006). How many drug targets are there? Nature Reviews Drug Discovery, 5(12):993-996.

Sicheri, F., Moarefi, I. & Kuriyan, J. (1997). Crystal structure of the Src family tyrosine kinase Hck. Nature, 385(6617):602.

Sladek, F.M. (2011). What are Nuclear Receptor Ligands? Molecular and Cellular Endocrinology, 334(1-2):3-13.

Van De Waterbeemd, H. & Gifford, E. (2003). ADMET in silico modelling: towards prediction paradise?. Nature Reviews Drug discovery, 2(3):192.

Veber, D.F., Johnson, S.R., Cheng, H.Y., Smith, B.R., Ward, K.W. & Kopple, K.D. (2002). Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry, 45(12):2615-2623.

Venkatesh, S. & Lipper, R.A. (2000). Role of the development scientist in compound lead selection and optimization. Journal of Pharmaceutical Sciences, 89(2):145-154.

Viegas-Junior, C., Danuello, A., Bolzani, V. S., Barreiro, E.J. & Fraga, C.A.M. (2007). Molecular hybridization: a useful tool in the design of new drug prototypes. Current Medicinal Chemistry, 14(17):1829-1852.

Wadhwa, R., Nigam, N., Bhargava, P., Dhanjal, J.K., Goyal, S., Grover, A., Sundar, D., Ishida, Y., Terao, K. & Kaul, S.C. (2016). Molecular characterization and enhancement of anticancer activity of caffeic acid phenethyl ester by γ cyclodextrin. Journal of Cancer, 7(13):1755.

Yamada, J. & Tomita, Y. (1996). Antimutagenic activity of caffeic acid and related compounds. Bioscience, Biotechnology, and Biochemistry, 60(2):328-329.

Yang, H., Lou, C., Sun, L., Li, J., Cai, Y., Wang, Z., Li, W., Liu, G. & Tang, Y. (2018). admetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties. Bioinformatics, 35(6):1067-1069.

Yee, S. (1997). In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man - fact or myth. Pharmaceutical Research, 14(6):763-766.



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