Article Sidebar

Download
PDF

Main Article Content

Abstract

QSAR analysis of the derivatives of thiadiazole and quinoxaline has been made for antiepileptic activity (pED50) using quantum mechanical and energy descriptors. The descriptors ionization potential, HOMO energy, LUMO energy, electron affinity, total energy, conformation minimum energy and log P have been used for QSAR analysis. The PM3 method has been employed for the calculation of descriptors. The best QSAR model has been obtained by using the descriptors electron affinity, total energy, conformation minimum energy and log P in which regression coefficient is 0.836651 and cross-validation coefficient is 0.761455. Also the single descriptor total energy is able to produce good QSAR model and hence the antiepileptic activity of any compound of the series can be predicted by calculating the value of total energy.

Keywords

Descriptors QSAR analysis PM3 method Antiepileptic activity Regression coefficient Cross-validation coefficient.

Article Details

License

Copyright (c) 2022 Asian Journal of Organic & Medicinal Chemistry

Creative Commons License

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

How to Cite
Kumar Mishra, D., Singh, A., Kumar Mishra, S., Singh, P., Singh, A., & Kumar, J. (2022). PM3 Method based QSAR Study of the Derivatives of Thiadiazole and Quinoxaline for Antiepileptic Activity using Quantum Mechanical and Energy Descriptors. Asian Journal of Organic & Medicinal Chemistry, 7(1), 111–122. https://doi.org/10.14233/ajomc.2022.AJOMC-P371
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. G.D. Hammer and S.J. McPhee, Pathophysiology of Disease: An Introduction to Clinical Medicine, McGraw-Hill Medical: New York, Ed. 6 (2010).
  2. T. Vos, C. Allen, M. Arora, R.M. Barber, Z.A. Bhutta, A. Brown, A. Carter, D.C. Casey, F.J. Charlson, A.Z. Chen, M. Coggeshall, L. Cornaby, L. Dandona, D.J. Dicker, T. Dilegge, H.E. Erskine, A.J. Ferrari, C. Fitzmaurice, T. Fleming, M.H. Forouzanfar, N. Fullman, P.W. Gething, E.M. Goldberg, N. Graetz, J.A. Haagsma, S.I. Hay, C.O. Johnson, N.J. Kassebaum, T. Kawashima, L. Kemmer, I.A. Khalil, Y. Kinfu, H.H. Kyu, J. Leung, X. Liang, S.S. Lim, A.D. Lopez, R. Lozano, L. Marczak, G.A. Mensah, A.H. Mokdad, M. Naghavi, G. Nguyen, E. Nsoesie, H. Olsen, D.M. Pigott, C. Pinho, Z. Rankin, N. Reinig, J.A. Salomon, L. Sandar, A. Smith, J. Stanaway, C. Steiner, S. Teeple, B.A. Thomas, C. Troeger, J.A. Wagner, H. Wang, V. Wanga, H.A. Whiteford, L. Zoeckler, A.A. Abajobir, K.H. Abate, C. Abbafati, K.M. Abbas, F. Abd-Allah, B. Abraham, I. Abubakar, L.J. Abu-Raddad, N.M.E. Abu-Rmeileh, I.N. Ackerman, A.O. Adebiyi, Z. Ademi, A.K. Adou, K.A. Afanvi, E.E. Agardh, A. Agarwal, A.A. Kiadaliri, H. Ahmadieh, O.N. Ajala, R.O. Akinyemi, N. Akseer, Z. Al-Aly, K. Alam, N.K.M. Alam, S.F. Aldhahri, M.A. Alegretti, Z.A. Alemu, L.T. Alexander, S. Alhabib, R. Ali, A. Alkerwi, F. Alla, P. Allebeck, R. Al-Raddadi, U. Alsharif, K.A. Altirkawi, N. Alvis-Guzman, A.T. Amare, A. Amberbir, H. Amini, W. Ammar, S.M. Amrock, H.H. Andersen, G.M. Anderson, B.O. Anderson, C.A.T. Antonio, A.F. Aregay, J. Ärnlöv, A. Artaman, H. Asayesh, R. Assadi, S. Atique, E.F.G.A. Avokpaho, A. Awasthi, B.P.A. Quintanilla, P. Azzopardi, U. Bacha, A. Badawi, K. Balakrishnan, A. Banerjee, A. Barac, S.L. Barker-Collo, T. Bärnighausen, L. Barregard, L.H. Barrero, A. Basu, S. Bazargan-Hejazi, E. Beghi, B. Bell, M.L. Bell, D.A. Bennett, I.M. Bensenor, H. Benzian, A. Berhane, E. Bernabé, B.D. Betsu, A.S. Beyene, N. Bhala, S. Bhatt, S. Biadgilign, K. Bienhoff, B. Bikbov, S. Biryukov, D. Bisanzio, E. Bjertness, J. Blore, R. Borschmann, S. Boufous, M. Brainin, A. Brazinova, N.J.K. Breitborde, J. Brown, R. Buchbinder, G.C. Buckle, Z.A. Butt, B. Calabria, I.R. Campos-Nonato, J.C. Campuzano, H. Carabin, R. Cárdenas, D.O. Carpenter, J.J. Carrero, C.A. Castañeda-Orjuela, J.C. Rivas, F. Catalá-López, J.-C. Chang, P.P.-C. Chiang, C.E. Chibueze, V.H. Chisumpa, J.-Y.J. Choi, R. Chowdhury, H. Christensen, D.J. Christopher, L.G. Ciobanu, M. Cirillo, M.M. Coates, S.M. Colquhoun, C. Cooper, M. Cortinovis, J.A. Crump, S.A. Damtew, R. Dandona, F. Daoud, P.I. Dargan, J. das Neves, G. Davey, A.C. Davis, D.D. Leo, L. Degenhardt, L.C.D. Gobbo, R.P. Dellavalle, K. Deribe, A. Deribew, S. Derrett, D.C.D. Jarlais, S.D. Dharmaratne, P.K. Dhillon, C. Diaz-Torné, E.L. Ding, T.R. Driscoll, L. Duan, M. Dubey, B.B. Duncan, H. Ebrahimi, R.G. Ellenbogen, I. Elyazar, M. Endres, A.Y. Endries, S.P. Ermakov, B. Eshrati, K. Estep, T.A. Farid, C.S.S. Farinha, A. Faro, M.S. Farvid, F. Farzadfar, V.L. Feigin, D.T. Felson, S.-M. Fereshtehnejad, J.G. Fernandes, J.C. Fernandes, F. Fischer, J.R.A. Fitchett, K. Foreman, F.G.R. Fowkes, J. Fox, R.C. Franklin, J. Friedman, J. Frostad, T. Fürst, N.D. Futran, B. Gabbe, P. Ganguly, F.G. Gankpé, T. Gebre, T.T. Gebrehiwot, A.T. Gebremedhin, J.M. Geleijnse, B.D. Gessner, K.B. Gibney, I.A.M. Ginawi, A.Z. Giref, M. Giroud, M.D. Gishu, G. Giussani, E. Glaser, W.W. Godwin, H. Gomez-Dantes, P. Gona, A. Goodridge, S.V. Gopalani, C.C. Gotay, A. Goto, H.N. Gouda, R. Grainger, F. Greaves, F. Guillemin, Y. Guo, R. Gupta, R. Gupta, V. Gupta, R.A. Gutiérrez, D. Haile, A.D. Hailu, G.B. Hailu, Y.A. Halasa, R.R. Hamadeh, S. Hamidi, M. Hammami, J. Hancock, A.J. Handal, G.J. Hankey, Y. Hao, H.L. Harb, S. Harikrishnan, J.M. Haro, R. Havmoeller, R.J. Hay, I.B. Heredia-Pi, P. Heydarpour, H.W. Hoek, M. Horino, N. Horita, H.D. Hosgood, D.G. Hoy, A.S. Htet, H. Huang, J.J. Huang, C. Huynh, M. Iannarone, K.M. Iburg, K. Innos, M. Inoue, V.J. Iyer, K.H. Jacobsen, N. Jahanmehr, M.B. Jakovljevic, M. Javanbakht, S.P. Jayaraman, A.U. Jayatilleke, S.H. Jee, P. Jeemon, P.N. Jensen, Y. Jiang, T. Jibat, A. Jimenez-Corona, Y. Jin, J.B. Jonas, Z. Kabir, Y. Kalkonde, R. Kamal, H. Kan, A. Karch, C.K. Karema, C. Karimkhani, A. Kasaeian, A. Kaul, N. Kawakami, P.N. Keiyoro, A.H. Kemp, A. Keren, C.N. Kesavachandran, Y.S. Khader, A.R. Khan, E.A. Khan, Y.-H. Khang, S. Khera, T.A.M. Khoja, J. Khubchandani, C. Kieling, P. Kim, C. Kim, D. Kim, Y.J. Kim, N. Kissoon, L.D. Knibbs, A.K. Knudsen, Y. Kokubo, D. Kolte, J.A. Kopec, S. Kosen, G.A. Kotsakis, P.A. Koul, A. Koyanagi, M. Kravchenko, B.K. Defo, B.K. Bicer, A.A. Kudom, E.J. Kuipers, G.A. Kumar, M. Kutz, G.F. Kwan, A. Lal, R. Lalloo, T. Lallukka, H. Lam, J.O. Lam, S.M. Langan, A. Larsson, P.M. Lavados, J.L. Leasher, J. Leigh, R. Leung, M. Levi, Y. Li, Y. Li, J. Liang, S. Liu, Y. Liu, B.K. Lloyd, W.D. Lo, G. Logroscino, K.J. Looker, P.A. Lotufo, R. Lunevicius, R.A. Lyons, M.T. Mackay, M. Magdy, A.E. Razek, M. Mahdavi, M. Majdan, A. Majeed, R. Malekzadeh, W. Marcenes, D.J. Margolis, J. Martinez-Raga, F. Masiye, J. Massano, S.T. McGarvey, J.J. McGrath, M. McKee, B.J. McMahon, P.A. Meaney, A. Mehari, F. Mejia-Rodriguez, A.B. Mekonnen, Y.A. Melaku, P. Memiah, Z.A. Memish, W. Mendoza, A. Meretoja, T.J. Meretoja, F.A. Mhimbira, A. Millear, T.R. Miller, E.J. Mills, M. Mirarefin, P.B. Mitchell, C.N. Mock, A. Mohammadi, S. Mohammed, L. Monasta, J.C.M. Hernandez, M. Montico, M.D. Mooney, M. Moradi-Lakeh, L. Morawska, U.O. Mueller, E. Mullany, J.E. Mumford, M.E. Murdoch, J.B. Nachega, G. Nagel, A. Naheed, L. Naldi, V. Nangia, J.N. Newton, M. Ng, F.N. Ngalesoni, Q.L. Nguyen, M.I. Nisar, P.M.N. Pete, J.M. Nolla, O.F. Norheim, R.E. Norman, B. Norrving, B.P. Nunes, F.A. Ogbo, I.-H. Oh, T. Ohkubo, P.R. Olivares, B.O. Olusanya, J.O. Olusanya, A. Ortiz, M. Osman, E. Ota, M. Pa, E.-K. Park, M. Parsaeian, V.M. de Azeredo Passos, A.J.P. Caicedo, S.B. Patten, G.C. Patton, D.M. Pereira, R. Perez-Padilla, N. Perico, K. Pesudovs, M. Petzold, M.R. Phillips, F.B. Piel, J.D. Pillay, F. Pishgar, D. Plass, J.A. Platts-Mills, S. Polinder, C.D. Pond, S. Popova, R.G. Poulton, F. Pourmalek, D. Prabhakaran, N.M. Prasad, M. Qorbani, R.H.S. Rabiee, A. Radfar, A. Rafay, K. Rahimi, V. Rahimi-Movaghar, M. Rahman, M.H.U. Rahman, S.U. Rahman, R.K. Rai, S. Rajsic, U. Ram, P. Rao, A.H. Refaat, M.B. Reitsma, G. Remuzzi, S. Resnikoff, A. Reynolds, A.L. Ribeiro, M.J.R. Blancas, H.S. Roba, D. Rojas-Rueda, L. Ronfani, G. Roshandel, G.A. Roth, D. Rothenbacher, A. Roy, R. Sagar, R. Sahathevan, J.R. Sanabria, M.D. Sanchez-Niño, I.S. Santos, J.V. Santos, R. Sarmiento-Suarez, B. Sartorius, M. Satpathy, M. Savic, M. Sawhney, M.P. Schaub, M.I. Schmidt, I.J.C. Schneider, B. Schöttker, D.C. Schwebel, J.G. Scott, S. Seedat, S.G. Sepanlou, E.E. Servan-Mori, K.A. Shackelford, A. Shaheen, M.A. Shaikh, R. Sharma, U. Sharma, J. Shen, D.S. Shepard, K.N. Sheth, K. Shibuya, M.-J. Shin, R. Shiri, I. Shiue, M.G. Shrime, I.D. Sigfusdottir, D.A.S. Silva, D.G.A. Silveira, A. Singh, J.A. Singh, O.P. Singh, P.K. Singh, A. Sivonda, V. Skirbekk, J.C. Skogen, A. Sligar, K. Sliwa, M. Soljak, K. Søreide, R.J.D. Sorensen, J.B. Soriano, L.A. Sposato, C.T. Sreeramareddy, V. Stathopoulou, N. Steel, D.J. Stein, T.J. Steiner, S. Steinke, L. Stovner, K. Stroumpoulis, B.F. Sunguya, P. Sur, S. Swaminathan, B.L. Sykes, C.E.I. Szoeke, R. Tabarés-Seisdedos, J.S. Takala, N. Tandon, D. Tanne, M. Tavakkoli, B. Taye, H.R. Taylor, B.J.T. Ao, B.A. Tedla, A.S. Terkawi, A.J. Thomson, A.L. Thorne-Lyman, A.G. Thrift, G.D. Thurston, R. Tobe-Gai, M. Tonelli, R. Topor-Madry, F. Topouzis, B.X. Tran, T. Truelsen, Z.T. Dimbuene, M. Tsilimbaris, A.K. Tura, E.M. Tuzcu, S. Tyrovolas, K.N. Ukwaja, E.A. Undurraga, C.J. Uneke, O.A. Uthman, C.H. van Gool, Y.Y. Varakin, T. Vasankari, N. Venketasubramanian, R.K. Verma, F.S. Violante, S.K. Vladimirov, V.V. Vlassov, S.E. Vollset, G.R. Wagner, S.G. Waller, L. Wang, D.A. Watkins, S. Weichenthal, E. Weiderpass, R.G. Weintraub, A. Werdecker, R. Westerman, R.A. White, H.C. Williams, C.S. Wiysonge, C.D.A. Wolfe, S. Won, R. Woodbrook, M. Wubshet, D. Xavier, G. Xu, A.K. Yadav, L.L. Yan, Y. Yano, M. Yaseri, P. Ye, H.G. Yebyo, P. Yip, N. Yonemoto, S.-J. Yoon, M.Z. Younis, C. Yu, Z. Zaidi, M.E.S. Zaki, H. Zeeb, M. Zhou, S. Zodpey, L.J. Zuhlke and C.J.L. Murray, Global, regional, and National Incidence, Prevalence, and Years Lived with Disability for 310 Diseases and Injuries, 1990–2015: A Systematic Analysis for the Global Burden of Disease Study 2015, Lancet, 388, 1545 (2016); https://doi.org/10.1016/S0140-6736(16)31678-6
  3. M.J. Eadie, Shortcomings in the Current Treatment of Epilepsy, Expert Rev. Neurother., 12, 1419 (2012); https://doi.org/10.1586/ern.12.129
  4. B.S. Chang and D.H. Lowenstein, Epilepsy, N. Engl. J. Med., 349, 1257 (2003); https://doi.org/10.1056/NEJMra022308
  5. R.S. Fisher, C. Acevedo, A. Bogacz, J.H. Cross, C.E. Elger, J. Engel Jr., L. Forsgren, A. Arzimanoglou, J.A. French, M. Glynn, D.C. Hesdorffer, B.I. Lee, G.W. Mathern, S.L. Moshé, E. Perucca, I.E. Scheffer, T. Tomson, M. Watanabe and S. Wiebe, ILAE Official Report: A Practical Clinical Definition of Epilepsy, Epilepsia, 55, 475 (2014); https://doi.org/10.1111/epi.12550
  6. S. Ghosh, J.K. Sinha, T. Khan, K.S. Devaraju, P. Singh, K. Vaibhav and P. Gaur, Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy, Biomedicines, 9, 470 (2021); https://doi.org/10.3390/biomedicines9050470
  7. R.S. Fisher, W. van Emde Boas, W. Blume, C. Elger, P. Genton, P. Lee and J. Engel Jr., Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE), Epilepsia, 46, 470 (2005); https://doi.org/10.1111/j.0013-9580.2005.66104.x
  8. M. Pandolfo, Genetics of Epilepsy, Semin. Neurol., 31, 506 (2011); https://doi.org/10.1055/s-0031-1299789
  9. E.M. Goldberg and D.A. Coulter, Mechanisms of Epileptogenesis: A Convergence on Neural Circuit Dysfunction, Nat. Rev. Neurosci., 14, 337 (2013); https://doi.org/10.1038/nrn3482
  10. D.L. Longo, 369 Seizures and Epilepsy, Harrison’s Principles of Internal Medicine, McGraw-Hill, Ed.: 18 (2012)
  11. G.K. Bergey, Neurostimulation in the Treatment of Epilepsy, Exp. Neurol., 244, 87 (2013); https://doi.org/10.1016/j.expneurol.2013.04.004
  12. S.P. Gupta, QSAR Studies on Enzyme Inhibitors, Chem. Rev., 87, 1183 (1987); https://doi.org/10.1021/cr00081a014
  13. T. Fujita and T. Ban, Structure-Activity Relation. 3. Structure-Activity Study of Phenethylamines as Substrates of Biosynthetic Enzymes of Sympathetic Transmitters, J. Med. Chem., 14, 148 (1971); https://doi.org/10.1021/jm00284a016
  14. C. Hansch and T. Fujita, p-s-p Analysis. A Method for the Correlation of Biological Activity and Chemical Structure, J. Am. Chem. Soc., 86, 1616 (1964); https://doi.org/10.1021/ja01062a035
  15. Y.C. Martin, J.B. Holland, C.H. Jarboe and N. Plotnikoff, Discriminant Analysis of the Relation Between Physical Properties and the Inhibition of Monoamine Oxidase by Aminotetralins and Aminoindans, J. Med. Chem., 17, 409 (1974); https://doi.org/10.1021/jm00250a008
  16. B.R. Kowalski and C.F. Bender, Pattern Recognition. Powerful Approach to Interpreting Chemical Data, J. Am. Chem. Soc., 94, 5632 (1972); https://doi.org/10.1021/ja00771a016
  17. K.C. Chu, Applications of Artificial Intelligence to Chemistry. Use of Pattern Recognition and Cluster Analysis to Determine the Pharmaco-logical Activity of Some Organic Compounds, Anal. Chem., 46, 1181 (1974); https://doi.org/10.1021/ac60345a030
  18. H. Levitan and J.L. Barker, Salicylate: A Structure-Activity Study of its Effects on Membrane Permeability, Science, 176, 1423 (1972); https://doi.org/10.1126/science.176.4042.1423
  19. P.P. Singh, F.A. Pasha and H.K. Srivastava, Novel Application of Softness Parameter for Regioselectivity and Reaction Mechanism, Indian J. Chem., 43B, 983 (2004).
  20. P.P. Singh, H.K. Srivastava and F.A. Pasha, DFT-based QSAR Study of Testosterone and its Derivatives, Bioorg. Med. Chem., 12, 171 (2004); https://doi.org/10.1016/j.bmc.2003.11.002
  21. P.P. Singh, F.A. Pasha and H.K. Srivastava, DFT Based Atomic Softness and Its Application in Site Selectivity, QSAR Comb. Sci., 22, 843 (2003); https://doi.org/10.1002/qsar.200330828
  22. J.M. Luco and F.H. Ferretti, QSAR Based on Multiple Linear Regression and PLS Methods for the Anti-HIV Activity of a Large Group of HEPT Derivatives, J. Chem. Inf. Comput. Sci., 37, 392 (1997); https://doi.org/10.1021/ci960487o
  23. J.B. Stanbury, J.B. Wyngaarden and D.S. Fredrickson, The Metabolic Basis of Inherited Disease, McGraw-Hill: New York, pp. 182-204 (1978).
  24. R.G. Parr, R.A. Donnelly, M. Levy and W.E. Palke, Electronegativity: The Density Functional Viewpoint, J. Chem. Phys., 68, 3801 (1978); https://doi.org/10.1063/1.436185
  25. M.C. Flanigan, A. Komornicki and J.W. McIver, Modern Theoretical Chemistry, Plenum Press: New York, vol. 8 (1977).
  26. M.J.S. Dewar and H.S. Rzepa, Ground States of Molecules. 45. MNDO Results for Molecules containing Beryllium, J. Am. Chem. Soc., 100, 777 (1978); https://doi.org/10.1021/ja00471a020
  27. R.G. Parr and R.G. Pearson, Absolute Hardness: Companion Parameter to Absolute Electronegativity, J. Am. Chem. Soc., 105, 7512 (1983); https://doi.org/10.1021/ja00364a005
  28. R.G. Parr, L.W. Szentpaly and S.J. Liu, Electrophilicity Index, J. Am. Chem. Soc. A, 121, 1922 (1999); https://doi.org/10.1021/ja983494x
  29. R. Hoffmann, Extended Hückel Theory—V: Cumulenes, Polyenes, Polyacetylenes and cn, Tetrahedron, 22, 521 (1966); https://doi.org/10.1016/0040-4020(66)80020-0
  30. R.S. Iczkowski and J.L. Margrave, Electronegativity, J. Am. Chem. Soc., 83, 3547 (1961); https://doi.org/10.1021/ja01478a001
  31. R.S. Mulliken, A New Electroaffinity Scale; Together with Data on Valence States and on Valence Ionization Potentials and Electron Affinities, J. Chem. Phys., 2, 782 (1934); https://doi.org/10.1063/1.1749394