MODELING OF ANTILEUKEMIC ACTIVITY FOR CARBOQUINONES USING QSAR METHODOLOGY
Keywords:
Modeling, QSAR, Anti-Leukemic activity, CarboquinonesAbstract
In the present study, Quantitative Structure Activity Relationship (QSAR) studies were performed on a series of Carboquinones derivatives as an anti-Leukemic agent. Stepwise multiple linear regression (MLR) analysis was applied to identify the structural requirement for anti-leukemic activity. The QSAR developed as a result of MLR indicate that the activity is affected by the Parachor, Refractive Index, logP and Pogliani index. The presence of Indicator parameter for amide group in the QSAR model shows the role of amide substitution on a parent structure in regulating anti – leukemic activity of the compounds. The results were further evaluated for its statistical significance and predictive power by cross validation method.
The information generated from the present study may be useful in the design of more potent carboquinones as an anti – leukemic ag
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Teh, J.S., Yano, T., and Rubin, H. (2007) Type II NADH:menaquinone oxidoreductase of Mycobacterium tuberculosis. Infect. Disord. Drug Targets 7(2), 169–181.
Srinivasan, K., Natarajan, D., Mohanasundari, C., Venkatakrishnan, C., and Nagamurugan, N. (2007) Antibacterial, preliminary phytochemical and pharmacognostical screening on the leaves of Vicoa indica (L.)DC. Iranian J.Pharmacol. Ther. 6(1), 109–113.
Wainwright, M. (2007) Natural product photoantimicrobials. Curr. Bioactive Compounds 3(4), 252–261.
Wang, P., Song, Y., Zhang, L., He, H., and Zhou, X. (2005) Quinone methide derivatives: important intermediates to DNA alkylating and DNA cross-linking actions. Curr. Med. Chem. 12(24), 2893–2913.
Bolognesi, M.L., Lizzi, F., Perozzo, R., Brun, R., and Cavalli, A. (2008) Synthesis of a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives bearing anti-trypanosomal and anti-leishmanial activity. Bioorg. Med. Chem. Lett. 18(7), 2272–2276.
Salem, M.M. and Werbovetz, K.A. (2006) Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis. Curr. Med. Chem. 13(21), 2571–2598.
Koyama, J. (2006) Anti-infective quinone derivatives of recent patents. Recent Pat. Antiinfect. Drug Discov. 1(1), 113–125.
Das Sarma, M., Ghosh, R., Patra, A., and Hazra, B. (2008) Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells. Eur. J. Med. Chem. 43(9), 1878– 1888.
He, J., Roemer, E., Lange, C., Huang, X., Maier, A., Kelter, G., Jiang, Y., Xu, L.-H., Menzel, K.-D., Grabley, S., Fiebig, H.-H., Jiang, C.-L., and Sattler, I. (2007) Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp. J. Med. Chem. 50(21), 5168–5175.
Petersen, S., Gauss, W., Kiehne, H., and Jüling, L. (1969) Derivatives of 2-amino-1,4 naphthoquinone as carcinostatic agents. Z. Krebsforsch. 72(2), 162–175.
Gough, J.D. and Hall, L.H. (1999) Modeling antileukemic activity of carboquinones with electrotopological state and chi indices. J. Chem. Inf. Comput. Sci. 39(2), 356–361.
Hodgson, J. Nat. Biotechnol., 2001, 19, 722-726.
Van de Waterbeemd, H.; Gifford, E. Nat. Rev. Drug Discov., 2003, 2, 192-204.
Proudfoot, J.R. Bioorg. Med. Chem. Lett., 2002, 12, 1647-1650.
Roche, O.; Schneider, P.; Zuegge, J.; Guba, W.; Kansy, M.; Alanine, A.; Bleicher, K.; Danel, F.; Gutknecht, E.M.; Rogers- Evans, M.; Neidhart, W.; Stalder, H.;, W.; Zimmermann, G.; Schneider, G. J. Med. Chem., 2002, 45, 137-142.
Pirard, B. Comb. Chem. High Throughput Screen., 2004, 7, 271- 280.
Croux C, Joossens K (2005) Influence of observations on the misclassification probability in quadratic discriminant analysis. J Multivar Anal 96:348-403
Devillers J (1996) Neuronal network in QSAR and drug design. Academic Press, London.
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