Electrophilic Group Chemical Potential as Sole DFT based Descriptor in a QSAR Model for Non-Nucleoside HIV-1 Reverse Transcriptase Inhibition Activity of a Series DABO Derivatives

Ananda Sarkar; Atish Dipankar Jana; Nabanita Giri

doi:10.14233/ajomc.2018.AJOMC-P150

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Abstract

The molecular modelling studies of a series of dihydroalkoxybenzyloxopyrimidine (DABO) derivatives have been undertaken by establishing a quantitative structure activity relationship (QSAR) model towards their reverse transcriptase activity. An efficient QSAR model based on a sole descriptor, namely 'group chemical potential' has been established. The QSAR model with this DFT based descriptor has a q² value 0.646 and r² value 0.650.

Keywords

Dihydroalkoxybenzyloxopyrimidine HIV-1 Reverse transcriptase inhibition QSAR Group chemical potential

How to Cite

Sarkar, A., Dipankar Jana, A., & Giri, N. (2018). Electrophilic Group Chemical Potential as Sole DFT based Descriptor in a QSAR Model for Non-Nucleoside HIV-1 Reverse Transcriptase Inhibition Activity of a Series DABO Derivatives. Asian Journal of Organic & Medicinal Chemistry, 3(4), 171–175. https://doi.org/10.14233/ajomc.2018.AJOMC-P150

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References

S.N. Lam, P. Acharya, R. Wyatt, P.D. Kwong and C.A. Bewley, Tyrosine-Sulfate Isosteres of CCR5 N-Terminus as Tools for Studying HIV-1 Entry, Bioorg. Med. Chem., 16, 10113 (2008); https://doi.org/10.1016/j.bmc.2008.10.005.
E.B. Kopp, J.J. Miglietta, A.G. Shrutkowski, C.K. Shih, P.M. Grob and M.T. Skoog, Steady State Kinetics and Inhibition of HIV-1 Reverse Transcriptase by a Non-Nucleoside Dipyridodiazepinone, BI-RG-587, using a Heteropolymeric Template, Nucleic Acids Res., 19, 3035 (1991); https://doi.org/10.1093/nar/19.11.3035.
T. Cihlar and A.S. Ray, Nucleoside and Nucleotide HIV Reverse Transcriptase Inhibitors: 25 years After Zidovudine, Antiviral Res., 85, 39 (2010); https://doi.org/10.1016/j.antiviral.2009.09.014.
M. Baba, H. Tanaka, E. De Clercq, R. Pauwels, J. Balza-rini, D. Schols, H. Nakashima, C.F. Perno, R.T. Walker and T. Miyasaka, Highly Specific Inhibition of Human Immunodeficiency Virus Type 1 by a Novel 6-Substituted Acyclouridine Derivative, Biochem. Biophys. Res. Commun., 165, 1375 (1989); https://doi.org/10.1016/0006-291X(89)92756-3.
Z. Debyser, R. Pauwels, K. Andries, J. Desmyter, M. Kukla, P.A. Janssen and E. De Clercq, An Antiviral Target on Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Revealed by Tetrahydroimidazo-[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -Thione Derivatives, Proc. Natl. Acad. Sci. USA, 88, 1451 (1991); https://doi.org/10.1073/pnas.88.4.1451.
D. Jochmans, J. Vingerhoets, E. Arnoult, L. Geeraert and J. Guillemont, Antiviral Research: Strategies in Antiviral Drug Discovery, In: Human Immunodeficiency Virus Type 1 Non-Nucleoside Reverse Transcriptase Inhibitors, ASM Press: Washington, Chap. 3, pp. 33-50 (2009).
O.J. D’cruz and F.M. Uckun, Novel Tight Binding PETT, HEPT and DABO-based Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase, J. Enzyme Inhib. Med. Chem., 21, 329 (2006); https://doi.org/10.1080/14756360600774413.
H. Kubinyi, QSAR Hansch Analysis and Related Approaches, VCH: Weinheim (1993).
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.
A. Sarkar and G. Mostafa, Towards the Design of Cyclooxygenase (COX) Inhibitors Based on 4¢,5-Disubstituted bIphenyl Acetic Acid Molecules: A QSAR Study with a New DFT Based Descriptor-Nucleus Independent Chemical Shift, J. Mol. Model., 15, 1221 (2009); https://doi.org/10.1007/s00894-009-0481-6.
R.G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, Oxford University Press: New York (1989).
A. Sarkar, T.R. Middya and A.D. Jana, A QSAR Study of Radical Scav-enging Antioxidant Activity of a Series of Flavonoids Using DFT Based Quantum Chemical Descriptors-The Importance of Group Frontier Electron Density, J. Mol. Model., 18, 2621 (2012); https://doi.org/10.1007/s00894-011-1274-2.
G. Job and F. Herrmann, Chemical Potential-A Quantity in Search of Recognition, Eur. J. Phys., 27, 353 (2006); https://doi.org/10.1088/0143-0807/27/2/018.
F. Reif, Fundamentals of Statistical and Thermal Physics, McGraw-Hill, New York (1965).
R.G. Parr, Density Functional Theory, Annu. Rev. Phys. Chem., 34, 631 (1983); https://doi.org/10.1146/annurev.pc.34.100183.003215.
R.G. Parr and W. Yang, Density-Functional Theory of the Electronic Structure of Molecules, Annu. Rev. Phys. Chem., 46, 701 (1995); https://doi.org/10.1146/annurev.pc.46.100195.003413.
H. Chermette, Chemical Reactivity Indexes in Density Functional Theory, J. Comput. Chem., 20, 129 (1999); https://doi.org/10.1002/(SICI)1096-987X(19990115)20:1<129::AID-JCC13>3.0.CO;2-A.
P. Geerlings, F. De Proft and W. Langenaeker, Conceptual Density Functional Theory, Chem. Rev., 103, 1793 (2003); https://doi.org/10.1021/cr990029p.
R.G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, Oxford University Press: Oxford (1989).
R.T. Sanderson, Chemical Bonds and Bond Energy, Academic Press: New York (1976).
R.T. Sanderson, Polar Covalence, Academic Press: New York (1961).
R.G. Parr and W. Yang, Density Functional Approach to the Frontier-Electron Theory of Chemical Reactivity, J. Am. Chem. Soc., 106, 4049 (1984); https://doi.org/10.1021/ja00326a036.
W. Yang and W.J. Mortier, The Use of Global and Local Molecular Parameters for the Analysis of the Gas-Phase Basicity of Amines, J. Am. Chem. Soc., 108, 5708 (1986); https://doi.org/10.1021/ja00279a008.
A. Mai, M. Artico, G. Sbardella, S. Massa, A.G. Loi, E. Tramontano, P. Scano and P. La Colla, Preparation and Anti-HIV-1 Activity of Thio Analogues of Dichydroalkoxybenzyloxopyrimidines, J. Med. Chem., 38, 3258 (1995); https://doi.org/10.1021/jm00017a010.
A. Mai, M. Artico, G. Sbardella, S. Quartarone, S. Massa, A.G. Loi, A. De Montis, F. Scintu, M. Putzolu and P. La Colla, Dihydro(alkylthio)-(naphthylmethyl)oxopyrimidines: Novel Non-Nucleoside Reverse Transcriptase Inhibitors of the S-DABO Series, J. Med. Chem., 40, 1447 (1997); https://doi.org/10.1021/jm960802y.
A. Mai, M. Artico, G. Sbardella, S. Massa, E. Novellino, G. Greco, A.G. Loi, E. Tramontano, M.E. Marongiu and P. La Colla, 5-Alkyl-2-(alkyl-thio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones: Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives, J. Med. Chem., 42, 619 (1999); https://doi.org/10.1021/jm980260f.
R. Ragno, A. Mai, G. Sbardella, M. Artico, S. Massa, C. Musiu, M. Mura, F. Marturana, A. Cadeddu and P. La Colla, Computer-Aided Design, Synthesis, and Anti-HIV-1 Activity in vitro of 2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as Novel Potent Non-Nucleoside Reverse Transcriptase Inhibitors, Also Active Against the Y181C Variant, J. Med. Chem., 47, 928 (2004); https://doi.org/10.1021/jm0309856.
A.D. Becke, Density-Functional Exchange-Energy Approximation with Correct Asymptotic Behavior, Phys. Rev. A, 38, 3098 (1988); https://doi.org/10.1103/PhysRevA.38.3098.
A.D. Becke, A New Mixing of Hartree–Fock and Local Density-Functional Theories, J. Chem. Phys., 98, 1372 (1993); https://doi.org/10.1063/1.464304.
A.D. Becke, Density-Functional Thermochemistry. III. The Role of Exact Exchange, J. Chem. Phys., 98, 5648 (1993); https://doi.org/10.1063/1.464913.
S. Hirata, C.G. Zhan, E. Apra, T.L. Windus and D.A. Dixon, A New, Self-Contained Asymptotic Correction Scheme To Exchange-Correlation Potentials for Time-Dependent Density Functional Theory, J. Phys. Chem. A, 107, 10154 (2003); https://doi.org/10.1021/jp035667x.
M. Sulpizi, G. Folkers, U. Rothlisberger, P. Carloni and L. Scapozza, Applications of Density Functional Theory-Based Methods in Medicinal Chemistry, Quant. Struct. Act. Relat., 21, 173 (2002); https://doi.org/10.1002/1521-3838(200207)21:2<173::AID-QSAR173>3.0.CO;2-B.
M. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.R. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski and D.J. Fox, Gaussian 09, Revision B.01, Gaussian Inc.: Wallingford, CT (2009).

References

S.N. Lam, P. Acharya, R. Wyatt, P.D. Kwong and C.A. Bewley, Tyrosine-Sulfate Isosteres of CCR5 N-Terminus as Tools for Studying HIV-1 Entry, Bioorg. Med. Chem., 16, 10113 (2008); https://doi.org/10.1016/j.bmc.2008.10.005.

E.B. Kopp, J.J. Miglietta, A.G. Shrutkowski, C.K. Shih, P.M. Grob and M.T. Skoog, Steady State Kinetics and Inhibition of HIV-1 Reverse Transcriptase by a Non-Nucleoside Dipyridodiazepinone, BI-RG-587, using a Heteropolymeric Template, Nucleic Acids Res., 19, 3035 (1991); https://doi.org/10.1093/nar/19.11.3035.

T. Cihlar and A.S. Ray, Nucleoside and Nucleotide HIV Reverse Transcriptase Inhibitors: 25 years After Zidovudine, Antiviral Res., 85, 39 (2010); https://doi.org/10.1016/j.antiviral.2009.09.014.

M. Baba, H. Tanaka, E. De Clercq, R. Pauwels, J. Balza-rini, D. Schols, H. Nakashima, C.F. Perno, R.T. Walker and T. Miyasaka, Highly Specific Inhibition of Human Immunodeficiency Virus Type 1 by a Novel 6-Substituted Acyclouridine Derivative, Biochem. Biophys. Res. Commun., 165, 1375 (1989); https://doi.org/10.1016/0006-291X(89)92756-3.

Z. Debyser, R. Pauwels, K. Andries, J. Desmyter, M. Kukla, P.A. Janssen and E. De Clercq, An Antiviral Target on Reverse Transcriptase of Human Immunodeficiency Virus Type 1 Revealed by Tetrahydroimidazo-[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -Thione Derivatives, Proc. Natl. Acad. Sci. USA, 88, 1451 (1991); https://doi.org/10.1073/pnas.88.4.1451.

D. Jochmans, J. Vingerhoets, E. Arnoult, L. Geeraert and J. Guillemont, Antiviral Research: Strategies in Antiviral Drug Discovery, In: Human Immunodeficiency Virus Type 1 Non-Nucleoside Reverse Transcriptase Inhibitors, ASM Press: Washington, Chap. 3, pp. 33-50 (2009).

O.J. D’cruz and F.M. Uckun, Novel Tight Binding PETT, HEPT and DABO-based Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase, J. Enzyme Inhib. Med. Chem., 21, 329 (2006); https://doi.org/10.1080/14756360600774413.

H. Kubinyi, QSAR Hansch Analysis and Related Approaches, VCH: Weinheim (1993).

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.

A. Sarkar and G. Mostafa, Towards the Design of Cyclooxygenase (COX) Inhibitors Based on 4¢,5-Disubstituted bIphenyl Acetic Acid Molecules: A QSAR Study with a New DFT Based Descriptor-Nucleus Independent Chemical Shift, J. Mol. Model., 15, 1221 (2009); https://doi.org/10.1007/s00894-009-0481-6.

R.G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, Oxford University Press: New York (1989).

A. Sarkar, T.R. Middya and A.D. Jana, A QSAR Study of Radical Scav-enging Antioxidant Activity of a Series of Flavonoids Using DFT Based Quantum Chemical Descriptors-The Importance of Group Frontier Electron Density, J. Mol. Model., 18, 2621 (2012); https://doi.org/10.1007/s00894-011-1274-2.

G. Job and F. Herrmann, Chemical Potential-A Quantity in Search of Recognition, Eur. J. Phys., 27, 353 (2006); https://doi.org/10.1088/0143-0807/27/2/018.

F. Reif, Fundamentals of Statistical and Thermal Physics, McGraw-Hill, New York (1965).

R.G. Parr, Density Functional Theory, Annu. Rev. Phys. Chem., 34, 631 (1983); https://doi.org/10.1146/annurev.pc.34.100183.003215.

R.G. Parr and W. Yang, Density-Functional Theory of the Electronic Structure of Molecules, Annu. Rev. Phys. Chem., 46, 701 (1995); https://doi.org/10.1146/annurev.pc.46.100195.003413.

H. Chermette, Chemical Reactivity Indexes in Density Functional Theory, J. Comput. Chem., 20, 129 (1999); https://doi.org/10.1002/(SICI)1096-987X(19990115)20:1<129::AID-JCC13>3.0.CO;2-A.

P. Geerlings, F. De Proft and W. Langenaeker, Conceptual Density Functional Theory, Chem. Rev., 103, 1793 (2003); https://doi.org/10.1021/cr990029p.

R.G. Parr and W. Yang, Density Functional Theory of Atoms and Molecules, Oxford University Press: Oxford (1989).

R.T. Sanderson, Chemical Bonds and Bond Energy, Academic Press: New York (1976).

R.T. Sanderson, Polar Covalence, Academic Press: New York (1961).

R.G. Parr and W. Yang, Density Functional Approach to the Frontier-Electron Theory of Chemical Reactivity, J. Am. Chem. Soc., 106, 4049 (1984); https://doi.org/10.1021/ja00326a036.

W. Yang and W.J. Mortier, The Use of Global and Local Molecular Parameters for the Analysis of the Gas-Phase Basicity of Amines, J. Am. Chem. Soc., 108, 5708 (1986); https://doi.org/10.1021/ja00279a008.

A. Mai, M. Artico, G. Sbardella, S. Massa, A.G. Loi, E. Tramontano, P. Scano and P. La Colla, Preparation and Anti-HIV-1 Activity of Thio Analogues of Dichydroalkoxybenzyloxopyrimidines, J. Med. Chem., 38, 3258 (1995); https://doi.org/10.1021/jm00017a010.

A. Mai, M. Artico, G. Sbardella, S. Quartarone, S. Massa, A.G. Loi, A. De Montis, F. Scintu, M. Putzolu and P. La Colla, Dihydro(alkylthio)-(naphthylmethyl)oxopyrimidines: Novel Non-Nucleoside Reverse Transcriptase Inhibitors of the S-DABO Series, J. Med. Chem., 40, 1447 (1997); https://doi.org/10.1021/jm960802y.

A. Mai, M. Artico, G. Sbardella, S. Massa, E. Novellino, G. Greco, A.G. Loi, E. Tramontano, M.E. Marongiu and P. La Colla, 5-Alkyl-2-(alkyl-thio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones: Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives, J. Med. Chem., 42, 619 (1999); https://doi.org/10.1021/jm980260f.

R. Ragno, A. Mai, G. Sbardella, M. Artico, S. Massa, C. Musiu, M. Mura, F. Marturana, A. Cadeddu and P. La Colla, Computer-Aided Design, Synthesis, and Anti-HIV-1 Activity in vitro of 2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as Novel Potent Non-Nucleoside Reverse Transcriptase Inhibitors, Also Active Against the Y181C Variant, J. Med. Chem., 47, 928 (2004); https://doi.org/10.1021/jm0309856.

A.D. Becke, Density-Functional Exchange-Energy Approximation with Correct Asymptotic Behavior, Phys. Rev. A, 38, 3098 (1988); https://doi.org/10.1103/PhysRevA.38.3098.

A.D. Becke, A New Mixing of Hartree–Fock and Local Density-Functional Theories, J. Chem. Phys., 98, 1372 (1993); https://doi.org/10.1063/1.464304.

A.D. Becke, Density-Functional Thermochemistry. III. The Role of Exact Exchange, J. Chem. Phys., 98, 5648 (1993); https://doi.org/10.1063/1.464913.

S. Hirata, C.G. Zhan, E. Apra, T.L. Windus and D.A. Dixon, A New, Self-Contained Asymptotic Correction Scheme To Exchange-Correlation Potentials for Time-Dependent Density Functional Theory, J. Phys. Chem. A, 107, 10154 (2003); https://doi.org/10.1021/jp035667x.

M. Sulpizi, G. Folkers, U. Rothlisberger, P. Carloni and L. Scapozza, Applications of Density Functional Theory-Based Methods in Medicinal Chemistry, Quant. Struct. Act. Relat., 21, 173 (2002); https://doi.org/10.1002/1521-3838(200207)21:2<173::AID-QSAR173>3.0.CO;2-B.

M. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.R. Montgomery Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P. Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski and D.J. Fox, Gaussian 09, Revision B.01, Gaussian Inc.: Wallingford, CT (2009).

Electrophilic Group Chemical Potential as Sole DFT based Descriptor in a QSAR Model for Non-Nucleoside HIV-1 Reverse Transcriptase Inhibition Activity of a Series DABO Derivatives

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