Modeling of Quinoacridinium Derivatives as Antitumor Agents using a QSAR analysis

Ruslin Hadanu


A QSAR analysis has been performed on a compound series of 1-11 quinoacridinium derivatives as internal test compounds, and compounds of 12-15 quinoacridinium derivatives as external test compounds. The electronic descriptors used in this study were atomic net charge (q), dipole moment (μ), ELUMO, EHOMO, polarizability (α), and Log P. They were calculated through HyperChem for Windows 8.0 software using semi-empirical PM3 method. The antitumor activity (IC50) of quinoacridinium derivative compounds was obtained from literature. Furthermore, the model of QSAR equation was analyzed through RML method which produced the best QSAR equation model: Log IC50 = -13.010 + 15.338(qC3) - 4.31(qC4) - 155.308(qC9) + 33.626(qC11) + 26.626(qC12) + 24.631(qC14) - 0.228(μ) - 0.621(ELUMO) - 0.066(α) + 0.233(Log P). The model of QSAR equation has a correlation coefficient n = 11, (r) = 1.00, (r2) = 1.00, SE = 0, and PRESS = 0.003. Among 28 compounds of quinoacridinium derivative which were designed, only 15 compounds, namely 16, 19-20, 22-28, 30-32, 39, and 40 compounds, have been recommended to be synthesized in the laboratory.


quinoacridinium derivatives, QSAR analysis, anti-tumor, PM3 method, MLR analysis

Full Text:



Alam, M., Khan, A., Wadood, A., Khan, A., Bashir, S., Aman, A., … Farooq, U. (2016). Bioassay-guided isolation of sesquiterpene coumarins from Ferula narthex bioss: A new anticancer agent. Frontiers in Pharmacology, 7(FEB), 1–6.

Bladt, T. T., Frisvad, J. C., Knudsen, P. B., & Larsen, T. O. (2013). Anticancer and antifungal compounds from Aspergillus, Penicillium and other filamentous fungi. Molecules (Vol. 18).

Bradley, C. J., Yabroff, K. R., Dahman, B., Feuer, E. J., Mariotto, A., & Brown, M. L. (2008). Productivity costs of cancer mortality in the United States: 2000-2020. Journal of the National Cancer Institute, 100(24), 1763–1770.

Cheng, M. K., Modi, C., Cookson, J. C., Hutchinson, I., Heald, R. A., McCarroll, A. J., … Stevens, M. F. G. (2008). Antitumor polycyclic acridines. 20.1 Search for DNA quadruplex binding selectivity in a series of 8,13-dimethylquino[4,3,2-kl]acridinium salts: Telomere-targeted agents. Journal of Medicinal Chemistry, 51(4), 963–975.

Cookson, J. C., Heald, R. A., & Stevens, M. F. G. (2005). Antitumor polycyclic acridines. 17. Synthesis and pharmaceutical profiles of pentacyclic acridinium salts designed to destabilize telomeric integrity. Journal of Medicinal Chemistry, 48(23), 7198–7207.

Deep, A., Narasimhan, B., Lim, S. M., Ramasamy, K., Mishra, R. K., & Mani, V. (2016). 4-Thiazolidinone derivatives: Synthesis, antimicrobial, anticancer evaluation and QSAR studies. RSC Advances, 6(111), 109485–109494.

Ferguson, A. M., Heritage, T., Jonathon, P., Pack, S. E., Phillips, L., Rogan, J., & Snaith, P. J. (1997). EVA: A new theoretically based molecular descriptor for use in QSAR/QSPR analysis. Journal of Computer-Aided Molecular Design, 11(2), 143–152.

Florea, A. M., & Büsselberg, D. (2011). Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers, 3(1), 1351–1371.

Fugmann, B., Steffan, B., and Steglich, W., (1984). Necatorone, An Alkaloidal Pigment From The Gilled Toadstool Lactarius Necator (Agaricales). Tetrahedron Letters, 25(33), 3575-3578.

Hadanu, R., Idris, S., & Sutapa, I. W. (2015). QSAR analysis of benzothiazole derivatives of antimalarial compounds based on AM1 semi-empirical method. Indonesian Journal of Chemistry, 15(1), 86–92.

Hadanu, R., & Syamsudin. (2013). Quantitative structure-activity relationship analysis of antimalarial compound of mangostin derivatives using regression linear approach. Asian Journal of Chemistry, 25(11), 6136–6140.

Hagan, D. J., Chan, D., Schwalbe, H., & Stevens, M. F. G. (1998). Antitumour polycyclic acridines . Part 3 . 1 A two-step conversion of 9-azidoacridine to 7 H -pyrido [ 4 , 3 , 2- kl ] acridines by Graebe – Ullmann thermolysis of substituted 9- ( 1 , 2 , 3-triazol-1-yl ) acridines, 915–923.

Hagan, D. J., Giménez-Arnau, E., Schwalbe, C. H., & Stevens, M. F. G. (1997). Antitumour polycyclic acridines. Part 1. Synthesis of 7H-pyrido- and 8H-quino-[4,3,2-kl]acridines by Graebe-Ullmann thermolysis of 9-(1,2,3-triazol-1-yl)acridines: Application of differential scanning calorimetry to predict optimum cyclisation conditions. Journal of the Chemical Society - Perkin Transactions 1, (18), 2739–2746.

Heliawati, L., Kardinan, A., Mayanti, T., & Tjokronegoro, R. ati. (2015). Piceatanol: Anti-cancer compound from Gewang seed extract. Journal of Applied Pharmaceutical Science, 5(1), 110–113.

Hosny, M. A., Radwan, H. A., & El-Sawi, E. A. (2012). Synthesis and anticancer activity of some new derivatives of coumarin and quinolinyl mercaptotriazoles. E-Journal of Chemistry, 9(4), 1737–1745.

Julino, M., & Stevens, M. F. G. (1998). Antitumour polycyclic acridines. Part 5.1Synthesis of 7H-pyrido[4,32-kl]acridines with exploitable functionality in the pyridine ring. Journal of the Chemical Society - Perkin Transactions 1, (10), 1677–1684.

Leonetti, C. (2004). Biological Activity of the G-Quadruplex Ligand RHPS4 (3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) Is Associated with Telomere Capping Alteration. Molecular Pharmacology, 66(5), 1138–1146.

Luo, Z.-H., He, S.-Y., Chen, B.-Q., Shi, Y.-P., Liu, Y.-M., Li, C.-W., & Wang, Q.-S. (2012). Synthesis and <i>in Vitro</i> Antitumor Activity of 1,3,4-Oxadiazole Derivatives Based on Benzisoselenazolone. Chemical & Pharmaceutical Bulletin, 60(7), 887–891.

Miladiyah, I., Tahir, I., Jumina, J., Mubarika, S., & Mustofa, M. (2016). Quantitative Structure-Activity Relationship Analysis of Xanthone Derivates as Cytotoxic Agents in Liver Cancer Cell Line HepG2. Molekul, 11(1), 143.

Missailidis, S., Stanslas, J., Modi, C., Ellis, M. J., Robins, R. A., Laughton, C. A., & Stevens, M. F. G. (2002). Antitumor Polycyclic Acridines . Part 12 . 1 Physical and Biological Properties A Lead Compound in Anticancer Drug Design, 13, 175–189.

Mota, L. F., Gaudio, A. C., and Takahata, Y., (2006). Quantitative Structure–Activity Relationships of a Series of Chalcone Derivatives (1,3–Diphenyl–2–propen–1–one) as Anti Plasmodium falciparum Agents (Anti Malaria Agents). Internet Electronic Journal of Molecular Design, 5(12), 555–569,

Noolvi, M. N., & Patel, H. M. (2013). Synthesis, method optimization, anticancer activity of 2,3,7-trisubstituted Quinazoline derivatives and targeting EGFR-tyrosine kinase by rational approach. 1st Cancer Update. Arabian Journal of Chemistry, 6(1), 35–48.

Nugraha, I., Annisa, A. N., Wibowo, A. T., & Kusuma, A. M. (2018). Chemopreventive Activity of Kola (Cola Accuminata) Seed Ethanol Extract in Mice Induced by Cyclophosphamide. IOP Conference Series: Materials Science and Engineering, 288(1).

Schmitt, S., & Dou, Q. P. (2013). Metal-Based Compounds as Proteasome-Inhibitory Anti-Cancer Drugs, 1(1), 1–3.

Shelton, J., Lu, X., Hollenbaugh, J. A., Cho, J. H., Amblard, F., & Schinazi, R. F. (2016). Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs. Chemical Reviews, 116(23), 14379–14455.

Stanslas, J., Hagan, D. J., Ellis, M. J., Turner, C., Carmichael, J., Ward, W., … Stevens, M. F. G. (2000). Antitumor polycyclic acridines. 7. Synthesis and biological properties of DNA affinic tetra- and pentacyclic acridines. Journal of Medicinal Chemistry, 43(8), 1563–1572.

Su, Q. G., Liu, Y., Cai, Y. C., Sun, Y. L., Wang, B., & Xian, L. J. (2011). Anti-tumour effects of xanthone derivatives and the possible mechanisms of action. Investigational New Drugs, 29(6), 1230–1240.

T. Reddy Prasad Reddy. (2012). Exploring the Anti-inflammatory and Anti-cancer compounds nfrom the leaves of Acalypha indica. IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS), 4(2), 01–07. Retrieved from

Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global Cancer Statistics, 2012. Cancer Statistics CA Cancer J Clin.

Tripodi, F., Pagliarin, R., Fumagalli, G., Bigi, A., Fusi, P., Orsini, F., … Coccetti, P. (2012). Synthesis and biological evaluation of 1,4-diaryl-2-azetidinones as specific anticancer agents: Activation of adenosine monophosphate activated protein kinase and induction of apoptosis. Journal of Medicinal Chemistry, 55(5), 2112–2124.



  • There are currently no refbacks.

Copyright (c) 2019 Indonesian Journal of Pharmacy

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:

analytics View My Stats