Influence of susceptibility to hydrolysis and hydrophobicity of arylsemicarbazones on their anti-nociceptive and anti-inflammatory activities

• Published in: European journal of medicinal chemistry 2012-04, Vol.50, p.140-148
• Main Authors: Vieira, Rafael P., Lessa, Josane A., Ferreira, Wallace C., Costa, Fernanda B., Bastos, Leandro F.S., Rocha, Willian R., Coelho, Márcio M., Beraldo, Heloisa
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics - chemistry; Analgesics - pharmacology; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Arylsemicarbazones; Benzaldehyde semicarbazone; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan - toxicity; Edema - chemically induced; Edema - drug therapy; Formaldehyde - toxicity; Hydrolysis; Hydrolysis - drug effects; Hydrophobic and Hydrophilic Interactions - drug effects; Inflammation; Male; Medical sciences; Mice; Molecular Structure; Motor Activity - drug effects; Neuropharmacology; Nociception; Pain - chemically induced; Pain - drug therapy; Pain Measurement; Pharmacology. Drug treatments; Rats; Rats, Wistar; Semicarbazide; Semicarbazones - chemical synthesis; Semicarbazones - chemistry; Semicarbazones - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.01.048

Benzaldehyde semicarbazone (BS) inhibited zymosan writhing response, carrageenan paw edema and both phases of formaldehyde nociceptive response. 2-hydroxybenzaldehyde semicarbazone (2-OHBS) and semicarbazide inhibited carrageenan paw edema and the second phase of formaldehyde nociceptive response. 2-OHBS inhibited zymosan writhing response. 3- and 4-OHBS did not show such activities. 2-OHBS showed the lowest LUMO energy, the highest contribution of the iminic carbon to LUMO energy, the highest positive charge on the iminic carbon, the highest negative charge on the iminic nitrogen and the highest susceptibility to hydrolysis. Hence semicarbazide may play important roles in 2-OHBS’s activities. Inhibition of the first phase of formaldehyde response by BS could be attributed to its higher hydrophobicity and lower susceptibility to hydrolysis in comparison to 2-OHBS. [Display omitted] ► Arylsemicarbazones were evaluated in models of pain and inflammation. ► Theoretical calculations were performed. ► 2-hydroxybenzaldehyde semicarbazone shows high susceptibility to hydrolysis. ► Semicarbazide may play an important role in semicarbazone’s activities. ► Benzaldehyde semicarbazone presents a distinct anti-nociceptive profile.