PA‑Int5: An isatin‑thiosemicarbazone derivative that exhibits anti‑nociceptive and anti‑inflammatory effects in Swiss mice

Da Fonseca,Aldilane Gonçalves; Fernandes Ribeiro Dantas,Luzia Leiros De Sena; Rodrigues,Joquebede Pereira; Alencar Filho,Marco Polo Da Costa; De Melo Rêgo,Moacyr Jesus Barreto; Da Rocha Pitta,Maira Galdino; De Moraes Gomes,Paulo André Teixeira; De Melo Silva,Vanessa Gouveia; Lima Leite,Ana Cristina; Furtado,Allanny Alves; Fernandes Pedrosa,Matheus De Freitas; Gavioli,Elaine Cristina; Moura Lemos,Telma Maria Araújo

doi:10.3892/br.2021.1437

PA‑Int5: An isatin‑thiosemicarbazone derivative that exhibits anti‑nociceptive and anti‑inflammatory effects in Swiss mice

Authors:
- Aldilane Gonçalves Da Fonseca
- Luzia Leiros De Sena Fernandes Ribeiro Dantas
- Joquebede Pereira Rodrigues
- Marco Polo Da Costa Alencar Filho
- Moacyr Jesus Barreto De Melo Rêgo
- Maira Galdino Da Rocha Pitta
- Paulo André Teixeira De Moraes Gomes
- Vanessa Gouveia De Melo Silva
- Ana Cristina Lima Leite
- Allanny Alves Furtado
- Matheus De Freitas Fernandes Pedrosa
- Elaine Cristina Gavioli
- Telma Maria Araújo Moura Lemos
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Affiliations: Research Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59012‑570, Brazil, Department of Biochemistry, Campus Universitário UFRN, Natal, Rio Grande do Norte 59064‑741, Brazil, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Pernambuco 50740‑521, Brazil, Department of Pharmacy Natal, Rio Grande do Norte 59012‑570, Brazil, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Campus Universitário UFRN, Natal, Rio Grande do Norte 59064‑741, Brazil
Published online on: May 26, 2021 https://doi.org/10.3892/br.2021.1437
Article Number: 61
Copyright: © Da Fonseca et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pain and inflammation are symptoms of various diseases, and they can be modulated by different pathways, thus highlighting the importance of investigating the therapeutic effects of novel compounds. Previous studies have shown that isatin‑thiosemicarbazone exhibits antitumor, antifungal antibacterial and other biological properties. Based on the wide range of biological effects of these compounds, the aim of the present study was to investigate the central nervous system (CNS) performance, and the anti‑nociceptive and anti‑inflammatory activity of (Z)‑2‑(5‑nitro‑2-oxoindolin‑3‑ilidene)‑N‑hydroazinecarbothioamide (PA‑Int5) in treated mice. Three doses of PA‑Int5 were tested orally (1.0, 2.5 and 5.0 mg/kg) in the nociceptive and inflammatory animal models. Additionally, the potential sedative effects of PA‑Int5 (5 mg/kg, oral gavage) were investigated using an open ﬁeld and rotarod tests, to exclude any possible unspecific effects of the nociceptive assays. Anti‑nociceptive activity was assessed using the acetic acid‑induced abdominal contortion and formalin tests, whereas anti‑inflammatory activity was assessed using a carrageenan‑induced paw edema and zymosan‑induced air‑pouch models. PA‑Int5 (5 mg/kg) induced anti‑nociceptive activity in the abdominal contortion model. In the formalin test, PA‑Int5 (at 2.5 and 5 mg/kg) reduced nociception in the second phase. At the higher dose tested, PA‑Int5 did not affect spontaneous locomotion or motor coordination. The data revealed that at all doses tested, the compound significantly reduced paw edema following carrageenan administration. In the zymosan‑induced air‑pouch model, PA‑Int5 potently inhibited leukocyte migration and protein levels at the site of inflammation. When combined, the results revealed, for the first time, that PA‑Int5 exhibited anti‑nociceptive and anti‑inflammatory activities, and highlights its potential, as well that of other derivatives, as novel candidates for pain relief.

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