Molecules 2012, 17(1), 809-819; doi:10.3390/molecules17010809
Article

Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents

Janaína V. dos Anjos 1 , Rajendra M. Srivastava 1 , João H. Costa-Silva 2 , Luciana Scotti 3 , Marcus T. Scotti 4 , Almir G. Wanderley 5 , Elisa Soares Leite 6 , Sebastião J. de Melo 7  and Francisco J. B. Mendonça Junior 8,* email
1 Departamento de Química Fundamental, Universidade Federal de Pernambuco, 50740-540, Recife, PE, Brazil 2 Núcleo de Educação Física e Ciências do Esporte, Universidade Federal de Pernambuco, 55608-680, Vitória de Santo Antão, PE, Brazil 3 Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Campus I, 50740-540, João Pessoa, PB, Brazil 4 Departamento de Engenharia e Meio Ambiente, Universidade Federal da Paraíba, Campus IV, 58297-000, Rio Tinto, PB, Brazil 5 Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil 6 Departamento de Engenharia Química, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil 7 Departamento de Antibióticos, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil 8 Departamento de Ciências Biológicas, Universidade Estadual da Paraíba, Campus V, 58058-420, João Pessoa, PB, Brazil
* Author to whom correspondence should be addressed.
Received: 27 October 2011; in revised form: 8 January 2012 / Accepted: 10 January 2012 / Published: 16 January 2012
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Abstract: In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a–i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.
Keywords: 4-(3H)-pyrimidinones; antinociceptive activity; molecular modeling; density functional theory

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MDPI and ACS Style

Anjos, J.V.; Srivastava, R.M.; Costa-Silva, J.H.; Scotti, L.; Scotti, M.T.; Wanderley, A.G.; Leite, E.S.; Melo, S.J.; Junior, F.J.B.M. Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents. Molecules 2012, 17, 809-819.

AMA Style

Anjos JV, Srivastava RM, Costa-Silva JH, Scotti L, Scotti MT, Wanderley AG, Leite ES, Melo SJ, Junior FJBM. Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents. Molecules. 2012; 17(1):809-819.

Chicago/Turabian Style

Anjos, Janaína V. dos; Srivastava, Rajendra M.; Costa-Silva, João H.; Scotti, Luciana; Scotti, Marcus T.; Wanderley, Almir G.; Leite, Elisa Soares; Melo, Sebastião J. de; Junior, Francisco J. B. Mendonça. 2012. "Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents." Molecules 17, no. 1: 809-819.

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