QSAR MODELING OF 2-[CH(OH)X]-5,8-(OY)2 -1,4-NAPHTHOQUININES AGAINST L1210 CELLS USING MULTIPLE LINEAR REGRESSION

Ajeet ., Brajpal Singh, Vipul Kumar

Abstract


Quinones are present in many drugs such as anthracyclines, daunorubicin,  doxorubicin,  mitomycin,  mitoxantrones  and saintopin, which are used clinically in the therapy of solid cancers. The  cytotoxic  effects  of  these  quinone  are  mainly  due  to  the inhibition  of  DNA  topoisomerase-II.  It  is  the  necessity  to  develop the  1,4-Naphthoquinone  analogues  with  Cytotoxic  effect.  Here  2-[CH(OH)X]-5,8-(OY)2-1,4-Naphthoquinines  analogues  have  been used  to  correlate  the  cytotoxic  activity  with  the  Eccentric Connectivity index (ECI), Fragment Complexity (FC) and McGowan Volumes  (MG)  for  studying  the  Quantitative  Structure  Activity Relationship  (QSAR).  Correlation  may  be  an  adequate  predictive model  which  can  help  to  provide  guidance  in  designing  and subsequently  yielding  greatly  specific  compounds  that  may  have reduced  side  effects  and  improved  pharmacological  activities.  We have  used  Multiple  Linear  Regression  (MLR),  one  of  the  best methods for developing the  QSAR model. Results from this QSAR study  have  suggested  that  ECI,  FC  and  MG  are  the  important descriptors for cytotoxic activities of 1,4-Naphthoquinones against L1210  cells.  For  the  validation  of  the  developed  QSAR  model, statistical  analysis  such  as  data  point-descriptor  ratio,  fraction  of variance,  cross  validation  test,  standard  deviation,  quality  factor, Fischer’s test; and internal validation such as Y-randomization test have been performed and all the tests validated this QSAR model.

Key  words:  1,4-Naphthoquinones,  QSAR,  Eccentric  connectivity  index, Fragment  complexity,  McGowan  Volume,  Multiple  Linear Regression

 


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References


Ajeet, 2012, QSAR modeling of recombinant human stromelysin inhibitors– MLR approach, Int. J. Adv. Pharm. Biol. Sci, 2(2), 171-175

Ajeet, Kumar, Vipul, Singh, and Brajpal, 2012, QSAR modeling of gelatinase inhibitors: MLR approach, Int. Res. J. Pharm., 3(3), 216-218

Arcamone, F., Cassinelli, G., 1998, Biosynthetic anthracyclines, Curr. Med. Chem., 5, 391–419

Begleiter, A., 2000, Clinical applications of quinone-containing alkylating agents, Front. Biosci., 5, E153–E171

Abhishek C., Dey, Pradip, Sen, Shantanu, Chetia, Pankaj, Choudhury Manabendra, Dutta, Dutta, Sharma G., 2012, An in silico appraisal of few bioactive compounds against kas-a for antitubercular drug efficacy, Asian. J. Pharm. Clin. Res., 5(1), 60-62

Di Marco, A., Cassinelli, G., Arcamone, and F., 1981, The discovery of daunorubicin, Cancer. Treat. Rep., 65, 3–8

Gregg, Siegal, and Eiso, A., B., 2007, Jan Schultz. Integration of fragment screening and library design, Drug Discovery Today, 12(23/24), 1032-1039

Lee, K. H., 1999, Novel antitumor agents from higher plants, Med. Res. Rev., 19, 569–596

Martyn, T., and Smith, 1985, Quinones as mutagens, carcinogens, and anticancer agents: Introduction and overview, J. Tox. Envir. Health., 16(5), DOI:10.1080/1528739850 9530776

McIntire, W. S., 1998, Newly discovered redox cofactors: possible nutritional, medical and pharmacological relevance to higher animals, Ann. Rev. Nutr., 18, 145–177

Meganathan, R., 2001, Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms, Vitam. Horm., 61, 173–218

Michael, H., Abraham, , Ibrahim A., and Andreas, M., Zissimos, 2004, Determination of sets of solute descriptors from chromatographic measurements, J. Chromatography, 1037, 29–47

Rajeshwar, P., Verma, 2006, Anti-Cancer Activities of 1,4-Naphthoquinones: A QSAR Study, Anti-Cancer Agents in Medicinal Chemistry, 6, 489-499

Sahu, Satish, Kohli, D., V., 2012, Banerjee Lopamudra 3D-QSAR Studies of Some Thiazolidinesdiones as Peroxisome Proliferator Activated Receptor (PPARγ) Agonist, Int. J. Pharm. Pharm. Sci., 4(1), 148-153

Sardana, S., and Madan, A., K., 2003, Topological models for prediction of antihypertensive activity of substituted benzylimidazoles, J. Mol. Struct. (Theochem), 638, 41-49

Sharma, Brij, Kishore, Singh, Prithvi, Sarbhai, Kirti, 2009, A QSAR Study on 5-HT7 Receptor Antagonists: Derivatives of (Phenylpiperazinyl-Alkyl) Oxindole, Int. J. Pharm. Pharm. Sc.i 1(1), 227-239

Verma, Rajeshwar, P., and Hansch, Corwin, 2010, QSAR modeling of taxane analogues against colon cancer, Eur. J. Med. Chem. 45, 1470-1477

Yap, C., W., 2011, PaDEL-descriptor: open source software to calculate molecular descriptors and fingerprints, J. Comput. Chem., 32(7), 1466-1474




DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp171-176

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