Design, synthesis and pharmacological assessment of new pyrazole compounds.
Jordana C OliveriaDaiany P B SilvaIziara F FlorentinoLidya C da SilvaGermán SanzBoniek G VazFrancine PaziniFlávio S de CarvalhoLuciano M LiãoThaís Rosa Marques Dos SantosMarize C ValadaresElson A CostaFernanda Cristina Alcantara Dos SantosBianca VillavicencioHugo VerliRicardo MenegattiPublished in: Inflammopharmacology (2020)
The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.
Keyphrases
- single cell
- induced apoptosis
- machine learning
- rheumatoid arthritis
- molecular dynamics
- neuropathic pain
- cell therapy
- electronic health record
- molecular docking
- stem cells
- peripheral blood
- molecular dynamics simulations
- cell cycle arrest
- spinal cord injury
- heart rate
- big data
- anti inflammatory
- endoplasmic reticulum stress
- mesenchymal stem cells
- cell proliferation
- protein protein
- blood pressure
- body composition