Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening
Abstract To evaluate the neuropharmacological profile of new spiro thiazepinone and thiazolidinone compounds in CD1 mice after a computer-aided virtual screening based on a GABA-A/BZD site. From a library of 240 pyrazolo[1,4]thiazepin-3-ones and 39 pyrimidinyl thiazolidin-4-ones, two molecular proto...
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Universidade de São Paulo
2025-01-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100803&lng=en&tlng=en |
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| author | Juan Sebastian Carrero-Sandoval Paola Andrea Cuervo-Prado Fabian Orozco-Lopez Christian Alonso Becerra-Rivas Estefany Arias-Quiroz Mario Francisco Guerrero-Pabón |
| author_facet | Juan Sebastian Carrero-Sandoval Paola Andrea Cuervo-Prado Fabian Orozco-Lopez Christian Alonso Becerra-Rivas Estefany Arias-Quiroz Mario Francisco Guerrero-Pabón |
| author_sort | Juan Sebastian Carrero-Sandoval |
| collection | DOAJ |
| description | Abstract To evaluate the neuropharmacological profile of new spiro thiazepinone and thiazolidinone compounds in CD1 mice after a computer-aided virtual screening based on a GABA-A/BZD site. From a library of 240 pyrazolo[1,4]thiazepin-3-ones and 39 pyrimidinyl thiazolidin-4-ones, two molecular prototypes of each series were selected by virtual screening using the rank consensus molecular docking approach, based on the GABA-A/BZD site. These compounds, coded as cpTP-0, cpTP-1, TAP-2 and cpTAP-2, were synthesised by multicomponent reactions and evaluated by neuropharmacological screening in CD1 mice (100 mg/kg, p.o.). The study revealed that cpTAP-2 exhibited a significant reduction of immobility time during the forced swimming test (FST), while it did not show any major effects in the rota-rod, open field, plus maze, tail suspension, pentylenetetrazole seizures, and barbiturate sleeping time tests. In a dose-response evaluation, cpTAP-2 reduced immobility time during forced swimming test in CD1 male mice at doses of 100 and 300 mg/kg with biologically relevant effect sizes. These results suggest that cpTAP-2 could elicit antidepressant effects possibly related to GABA-A/benzodiazepine site, although other mechanisms could be implicated. |
| format | Article |
| id | doaj-art-d40e2397413f4cd1ad1b5132507e7783 |
| institution | Kabale University |
| issn | 2175-9790 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj-art-d40e2397413f4cd1ad1b5132507e77832025-01-21T07:42:21ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902025-01-016110.1590/s2175-97902025e24066Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screeningJuan Sebastian Carrero-Sandovalhttps://orcid.org/0009-0006-5516-7029Paola Andrea Cuervo-Pradohttps://orcid.org/0000-0003-4957-2811Fabian Orozco-Lopezhttps://orcid.org/0000-0003-4553-9985Christian Alonso Becerra-Rivashttps://orcid.org/0000-0002-9662-3813Estefany Arias-Quirozhttps://orcid.org/0009-0006-9530-4913Mario Francisco Guerrero-Pabónhttps://orcid.org/0000-0003-1789-1818Abstract To evaluate the neuropharmacological profile of new spiro thiazepinone and thiazolidinone compounds in CD1 mice after a computer-aided virtual screening based on a GABA-A/BZD site. From a library of 240 pyrazolo[1,4]thiazepin-3-ones and 39 pyrimidinyl thiazolidin-4-ones, two molecular prototypes of each series were selected by virtual screening using the rank consensus molecular docking approach, based on the GABA-A/BZD site. These compounds, coded as cpTP-0, cpTP-1, TAP-2 and cpTAP-2, were synthesised by multicomponent reactions and evaluated by neuropharmacological screening in CD1 mice (100 mg/kg, p.o.). The study revealed that cpTAP-2 exhibited a significant reduction of immobility time during the forced swimming test (FST), while it did not show any major effects in the rota-rod, open field, plus maze, tail suspension, pentylenetetrazole seizures, and barbiturate sleeping time tests. In a dose-response evaluation, cpTAP-2 reduced immobility time during forced swimming test in CD1 male mice at doses of 100 and 300 mg/kg with biologically relevant effect sizes. These results suggest that cpTAP-2 could elicit antidepressant effects possibly related to GABA-A/benzodiazepine site, although other mechanisms could be implicated.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100803&lng=en&tlng=enAntidepressantDrug designVirtual screeningSpirothiazolidinoneGABA-A/BZD receptor |
| spellingShingle | Juan Sebastian Carrero-Sandoval Paola Andrea Cuervo-Prado Fabian Orozco-Lopez Christian Alonso Becerra-Rivas Estefany Arias-Quiroz Mario Francisco Guerrero-Pabón Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening Brazilian Journal of Pharmaceutical Sciences Antidepressant Drug design Virtual screening Spirothiazolidinone GABA-A/BZD receptor |
| title | Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| title_full | Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| title_fullStr | Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| title_full_unstemmed | Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| title_short | Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| title_sort | neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening |
| topic | Antidepressant Drug design Virtual screening Spirothiazolidinone GABA-A/BZD receptor |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100803&lng=en&tlng=en |
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