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ETA index in QSAR

 

Quantitative structure-activity relationships (QSARs) represent predictive models derived from application of statistical tools correlating biological activity (including therapeutic and toxic) or other properties of chemicals (drugs/toxicants/environmental pollutants) with descriptors representative of molecular structure and/or property. QSARs are being applied in many disciplines like risk assessment, toxicity prediction, property prediction, and regulatory decisions apart from drug discovery and lead optimization.

 
Topological descriptors are derived from hydrogen-suppressed molecular graphs, in which the atoms are represented by vertices and the bonds by edges. The connections between the atoms can be described by various types of topological matrices (e.g., distance or adjacency matrices), which can be mathematically manipulated so as to derive a single number, usually known as graph invariant, graph-theoretical index or topological index (TI) . In consequence, the TIs can be defined as two-dimensional descriptors that can be easily calculated from the molecular graphs, and do not depend on the way the graph is depicted or labeled and no need of energy minimization of the chemical structure.

 

The Drug Theoretics Laboratory of the Department of Pharmaceutical Technology, Jadavpur University, has developed a new set of chemical descriptors termed as extended topochemical atom (ETA) indices which can be used for predictive modeling of various activities/toxicities/properties (endpoints) having applications in drug design, predictive toxicology and chemical engineering sciences. The ETA descriptors have been developed based on modification of TAU descriptors, which were originally introduced at this University in late eighties (Indian J. Chem. 27B, 1988, 734–739). Various ETA indices try to capture chemical information of organic compounds covering multidimensional aspects like hydrophobicity, electronic factors, size and shape factors etc.  The ETA indices have been used in QSAR studies for various endpoints covering toxicity and physicochemical properties and it has been found that the models developed from ETA indices are better or at least comparable in statistical quality to those developed from other non-ETA topological indices. This confirms that ETA indices are sufficiently rich in encoding chemical information and these can be used extensively in QSAR studies for predictive modeling of various activity/toxicity/property endpoints.

 

Some of the basic descriptors defined under the extended topochemical atom (ETA) indices scheme originally developed by our group have been incorporated in the new version (version 6) of the popular software package DRAGON (TALETE srl, Italy). See http://www.talete.mi.it/products/dragon_molecular_descriptors.htm and http://www.talete.mi.it/help/dragon_help/index.html

 

The ETA descriptors have also been included in the authoritative book entitled Molecular Descriptors for Chemoinformatics by R. Todeschini, V. Consonni and R. Mannhold (Wiley, 2009). See http://as.wiley.com/WileyCDA/WileyTitle/productCd-3527318526.html

 

Many of the first and second generation ETA indices are now available for computation in version 2.11 of PaDEL-Descriptor (Yap, 2011), an open source software available at http://padel.nus.edu.sg/software/padeldescriptor

 

Wide applications of the ETA indices in QSAR/QSPR/QSTR analyses are solicited.

 

 

 

Relevant publications on ETA indices:

1.*           Roy K & Ghosh G, Introduction of Extended Topochemical Atom (ETA) Indices in the Valence Electron Mobile (VEM) Environment as Tools for QSAR/QSPR Studies, Internet Electron J Mol Des, 2, 2003, 599-620, http://www.biochempress.com/av02_0599.html .

2.*           Roy K & Ghosh G, QSTR with Extended Topochemical Atom Indices. 2. Fish Toxicity of Substituted Benzenes. J. Chem. Inf. Comput. Sci., 44, 2004, 559-567. http://dx.doi.org/10.1021/ci0342066 .

3.*           Roy K & Ghosh G, QSTR with Extended Topochemical Atom Indices. 3. Toxicity of Nitrobenzenes to Tetrahymena pyriformis. QSAR Comb Sci, 23, 2004, 99-108.  http://dx.doi.org/10.1002/qsar.200330864 .

4.*           Roy K & Ghosh G, QSTR with Extended Topochemical Atom Indices. 4. Modeling of the Acute Toxicity of Phenylsulfonyl Carboxylates to Vibrio fischeri Using Principal Component Factor Analysis and Principal Component Regression Analysis. QSAR Comb Sci, 23, 2004, 526-535. http://dx.doi.org/10.1002/qsar.200430891   

5.*           Roy K & Ghosh G, QSTR with Extended Topochemical Atom Indices. Part 5. Modeling of the Acute Toxicity of Phenylsulfonyl Carboxylates to Vibrio fischeri Using Genetic Function Approximation. Bioorg Med. Chem., 13, 2005, 1185-1194. http://dx.doi.org/10.1016/j.bmc.2004.11.014

6.*           Roy K and Ghosh G, QSTR with extended topochemical atom (ETA) indices. VI. Acute toxicity of benzene derivatives to tadpoles (Rana japonica).  J. Mol. Model, 12,  2006, 306-316, http://dx.doi.org/10.1007/s00894-005-0033-7 .

7.*           Roy K and Sanyal I., QSTR with Extended Topochemical Atom Indices. 7.QSAR of Substituted Benzenes to Saccharomyces cerevisiae. QSAR Comb Sci, 25, 2006, 359-371. http://dx.doi.org/10.1002/qsar.200530172 .

8.*           Roy K & Ghosh G, QSTR with extended topochemical atom (ETA) indices. 8. QSAR for the inhibition of substituted phenols on germination rate of Cucumis sativus using chemometric tools. QSAR Comb Sci, 25, 2006, 846-859. http://dx.doi.org/10.1002/qsar.200510211 .

9.*           Roy K & Ghosh G, QSTR with extended topochemical atom (ETA)  indices. 9. Comparative QSAR for the toxicity of diverse functional organic compounds to Chlorella  vulgaris using chemometric tools. Chemosphere, 70, 2007, 1-12. http://dx.doi.org/10.1016/j.chemosphere.2007.07.037

10.*   Roy K, Sanyal I and Roy P P, QSPR of the Bioconcentration Factors of Nonionic Organic Compounds in Fish using Extended Topochemical Atom (ETA) Indices. SAR QSAR Environ Res, 17, 2006, 563-582. http://dx.doi.org/10.1080/10629360601033499 .

11.*    Roy K, Sanyal I and Ghosh G, QSPR of n-Octanol/Water Partition Coefficient of Nonionic Organic Compounds Using Extended Topochemical Atom (ETA) Indices. QSAR Comb Sci, 25, 2006, 629-646, http://dx.doi.org/10.1002/qsar.200610112 .

12.*         Roy K & Ghosh G, QSTR with Extended Topochemical Atom (ETA) Indices. 10. Modeling of Toxicity of Organic Chemicals to Humans Using Different Chemometric Tools. Chem Biol Drug Des, 72, 2008, 383-394, http://dx.doi.org/10.1111/j.1747-0285.2008.00712.x

13.*         Roy K, Ghosh G, QSTR with extended topochemical atom (ETA) indices. 11. Comparative QSAR of acute NSAID cytotoxicity in rat hepatocytes using chemometric tools. Molecular Simulation, 35, 2009, 648-659, http://dx.doi.org/10.1080/08927020902744664

14.*         Roy K, Ghosh G, QSTR with extended topochemical atom (ETA) indices. 12. QSAR for the toxicity of diverse aromatic compounds to Tetrahymena pyriformis using chemometric tools. Chemosphere, 77, 2009, 999-1009, http://dx.doi.org/10.1016/j.chemosphere.2009.07.072

15.*         Roy K, Ghosh G, QSTR with extended topochemical atom (ETA) Indices. 13. Modeling of hERG K+ channel blocking activity of diverse functional drugs using different chemometric tools. Molecular Simulation, 15, 2009, 1256-1268, http://dx.doi.org/10.1080/08927020903015379

16.*        Roy K, Das RN, QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis. J Hazard Mater 183, 2010, 913-922, http://dx.doi.org/10.1016/j.jhazmat.2010.07.116  

17.*        Roy K, Ghosh G, Exploring QSARs with Extended Topochemical Atom (ETA) Indices for Modeling Chemical and Drug Toxicity. Current Pharm Des, 16, 2010, 2625-2639, http://www.benthamdirect.org/pages/b_viewarticle.php?3161953

18.*   Roy K, Das R N, On some novel extended topochemical atom (ETA) parameters for effective encoding of chemical information and modeling of fundamental physicochemical properties. SAR QSAR Environ Res 22, 2011, 451-472, http://dx.doi.org/10.1080/1062936X.2011.569900

19.*    Roy K, Das RN, QSTR with extended topochemical atom (ETA) indices. 15. Development of predictive models for toxicity of organic chemicals against fathead minnow using second generation ETA indices. SAR QSAR Environ Res 2011 (In press), http://dx.doi.org/10.1080/1062936X.2011.645872

20.* Roy K, Das RN, On Extended Topochemical Atom (ETA) Indices for QSPR Studies. In: Advanced Methods and Applications in Chemoinformatics: Research Progress and New Applications (E A Castro, A K Hagi, Eds.) IGI Global, PA, 2011, pp. 380-411, http://www.igi-global.com/bookstore/chapter.aspx?titleid=56464

 

Updated on January 02, 2012

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