| A Combined study using Ligand-based Design, Synthesis and Pharmacological evaluation of analogues of the Acetaminophen ortho-Regioisomer with potent Analgesic Activity. | |
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MedLine Citation:
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PMID: 22404983 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A ligand-based drug design study was performed to acetaminophen regioisomers as analgesic candidates employing quantum chemical calculations at the DFT/B3LYP level of theory and the 6-31G* basis set. To do so, many molecular descriptors were used such as HOMO, ionization potential, H-O bond dissociation energies and spin densities, which might be related with quench reactivity of the tyrosyl radical to give N-acetyl-p-benzosemiquinone-imine (NAPSQI) through an initial electron withdrawing or hydrogen atom abstraction. Based on this in silico work, the most promising molecule, orthobenzamol (OBZ), was synthesized and tested. The results expected from the theoretical prediction were confirmed in vivo using mouse models of nociception such as writhing, paw licking and hot plate tests. All biological results suggested an antinociceptive activity mediated by opioid receptors. Furthermore, at 90 and 120 min, this new compound had an effect that was comparable to morphine, the standard drug for this test. Finally, the pharmacophore model is discussed according to the electronic properties derived from quantum chemistry calculations. © 2012 John Wiley & Sons A/S. |
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Authors:
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Luana M D Queiroz; Josmar R Rocha; Andrei Leitão; Carlos A Montanari; Albérico B F da Silva; Pergentino J C Sousa; Rosivaldo S Borges |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-8 |
Journal Detail:
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Title: Chemical biology & drug design Volume: - ISSN: 1747-0285 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101262549 Medline TA: Chem Biol Drug Des Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 John Wiley & Sons A/S. |
Affiliation:
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Programa de Pós-Graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Universidade Federal do Pará, Augusto Correa, SN, 66075-110, Belém, PA, Brazil. Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, 13560-970, São Carlos-SP, Brazil. |
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