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KMID : 0043320120350101713
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Archives of Pharmacal Research
2012 Volume.35 No. 10 p.1713 ~ p.1722
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Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: Antinociceptive activity, molecular modeling and In Silico ADMET screening
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Oliveira Kely N.
Souza Marcia M.
Sathler Plinio Cunha
Magalhaes Uiaran O.
Rodrigues Carlos R.
Castro Helena C.
Palm Patricia R.
Sarda Maicon
Perotto Pablo E.
Cezar Sabrina
Brito Monique A.
Ferreira Ariane S. S. R.
Cabral Lucio Mendes
Machado Clodoaldo
Nunes Ricardo J.
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Abstract
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In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID50 = 5.1 and 6.8 μmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski “rule-of-five”, which is theoretically important for good drug absorption and permeation.
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KEYWORD
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Sulphonylhydrazones, Sulphonamides, Analgesic activity, SAR, ADMET
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