Neuropharmacological profile of new thiazepinone and thiazolidinone compounds designed by virtual screening

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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Main Authors: Juan Sebastian Carrero-Sandoval, Paola Andrea Cuervo-Prado, Fabian Orozco-Lopez, Christian Alonso Becerra-Rivas, Estefany Arias-Quiroz, Mario Francisco Guerrero-Pabón
Format: Article
Language:English
Published: Universidade de São Paulo 2025-01-01
Series:Brazilian Journal of Pharmaceutical Sciences
Subjects:
Antidepressant
Drug design
Virtual screening
Spirothiazolidinone
GABA-A/BZD receptor
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100803&lng=en&tlng=en
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Summary: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.
ISSN:2175-9790

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