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Document Type : Research Paper


1 2nd 200 Housing Estate, Rock Garden Avenue

2 Department of Chemistry, Federal University Lokoja, Nigeria

3 Department of Science Laboratory Technology, Osun State College of Technology, Esa-Oke, Nigera

4 Department of Chemistry, Federal College of Education Kastina, P.M.B. 2041, Kastina Nigeria


Hepatocellular carcinoma is the fourth most common cause of cancer related fatality globally and has constituted a serious health care burden owing to dearth of effective systemic chemotherapeutic agents against this disease. In this study, a set of bioactive compounds with proven anticancer activities against HepG2 cell lines were subjected to theoretical investigations via the use of QSAR modelling, molecular docking simulation, ADMET and drug-likeness evaluation. The validated QSAR model (R2 = 0.94, R2Adj = 0.93, Q2LOO = 0.91, R2Pred = 0.81) revealed the predominant influence of ZMIC2 descriptor on the chemotherapeutic properties of the compounds. Optimization of the anticancer property of the most active compound (template) through its structural modification guided by ZMIC2 descriptor in the model led to the design of more potent analogues; G-1, G-2, and G-3 with predicted IC50 value of 9.77 µM, 2.45 µM, and 5.50 µM, respectively. Molecular docking investigation of the designed ligands against the active sites of Aurora B kinase, the protein target found to be strongly involved in hepatocarcinogenesis, reveals that G-1, G-2, and G-3 bind with ΔG value of -8.0 kcal/mol, -7.8 kcal/mol, and -7.7 kcal/mol, respectively. These values are higher and better compared to -7.5 kcal/mol recorded for the template molecule. Also, insilico drug-likeness and ADMET assessment of the novel ligands revealed that they possess good oral bioavailability, excellent pharmacokinetic and toxicity profiles. However, further invivo and invitro studies are required on the designed drug candidates to validate these claims.


[1] International Agency for Research on Cancer; https://www.
[2] I. Ali, F. Batool, S. A. Z. Naqvi, A. Islam, S. M. Osman, A. Nocentini, S. A. Alissa, C. T. Supuran, J. Enz. Inhib. Med. Chem., 35(1), 265 (2019).
[3] C. Verslype, O. Rosmorduc, P. Rougier. Ann Oncol 23, 41 (2012).
[4] J.D. Yang, P. Hainaut, G.J. Gores, A. Amadou, A. Plymoth, L.R. Roberts. Nat. Rev. Gastroenterol. Hepatol., 16, 589 (2019).
[5] P. Rawla, T. Sunkara, P. Muralidharan, J.P. Raj. Contemp. Oncol., 22, 141 (2018).
[6] K.A. McGlynn, W.T. London. Clin. Liver Dis., 15, 223 (2011).
[7] F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal. CA Cancer J. Clin., 68, 394 (2018).
[8] L. Kulik, H.B. El-Serag. Gastroenterology, 156, 477 (2019).
[9] M. Kudo. Liver Cancer, 7, 134 (2018).
[10] J. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, et al. N Engl J Med., 359, 378 (2018).
[11] A. Cheng, Y. Kang, Z. Chen, C. Tsao, S. Qin, et al. Lancet Oncol., 10, 25 (2009).
[12] M. Shaharyar, M.M. Abdullah, M.A. Bakht. Eur J Med Chem., 45, 114 (2010).
[13] M. Hranjec, K. Starcevic, S.K. Pavelic, P. Lucin, K. Pavelic, G.K. Zamola. Eur J Med Chem., 46, 2274 (2011).
[14] H.T. Abdel-Mohsen, F.A.F. Ragab, M.M. Ramla, H.I. El Diwani. Eur J Med Chem, 45, 2336 (2010).
[15] M. Rahman, A.A. Siddiqui. Int J Pharm Sci Drug Res, 2 (3), 165 (2010).
[16] M.M. Ramla, M.A. Omar, A.M.M. El-Khamry, H.I. El-Diwani. Bioorg Med Chem, 14, 7324 (2006).
[17] M.M. Ramla, M.A. Omar, H. Tokuda, H.I. El-Diwani. Bioorg Med Chem., 15, 6489 (2007).
[18] H.M. Refaat. Eur J Med Chem, 45, 2949 (2010).
[19] H.L. Qin, J. Leng, B.G. Youssif, M.W. Amjad, M.A.G. Raja, M.A. Hussain, et al. Chemical biology & drug design. 90(3), 443 (2017).
[20] Y.Y. Xu, Y. Cao, H. Ma, H.Q. Li, G.Z. Ao. Bioorganic &