Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68023, 21944-971, Rio de Janeiro, RJ, Brazil.
Published: June 2004
AI Article Synopsis
Article Abstract
In this work, we reported the synthesis and evaluation of the analgesic, antiinflammatory, and antiplatelet properties of new phenothiazine-attached acylhydrazone derivatives (6), designed exploring the molecular hybridization approach between antipsychotic chlorpromazine (4) and other heterocyclic derivatives (3) and (5) developed at LASSBio. Target compounds were synthesized in very good yields exploiting diphenylamine (7) as starting material, through regioselective functionalization of the C-1 position of 10H-phenothiazine ring. The evaluation of platelet antiaggregating profile lead us to identify a new potent prototype of antiplatelet derivative, that is (6a) (IC(50)=2.3 microM), which acts in arachidonic acid pathway probably by inhibition of platelet COX-1 enzyme. Additionally, the change of para-substituent group of acylhydrazone framework permitted us to identify hydrophilic carboxylate derivative (6g) and hydrophobic bromo derivative (6b) as two new leads of analgesics more active than dipyrone used as standard and with selective peripheral or central mechanism of action.
Mutations in KRAS G12C are among the more common oncogenic driver mutations in non-small cell lung cancer (NSCLC). In December 2022, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib, a small molecule covalent inhibitor of KRAS G12C, for the treatment of patients with locally advanced or metastatic KRAS G12C mutant NSCLC who received at least one prior systemic therapy based on promising results from phase 1 and 2 trials wherein adagrasib demonstrated a median PFS of 6.5 months.
One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.
The privileged fused-ring system comprising the bicyclo[2.2.2]diazaoctane (BDO) core is prevalent in diketopiperazine (DKP) natural products with potent and diverse biological activities, with some being explored as drug candidates.
Introduction: Lung injury, a common complication of sepsis, arises from elevated reactive oxygen species (ROS), mitochondrial dysfunction, and cell death driven by inflammation. In this study, a novel class of ultrasmall nanoparticles (CuO USNPs) was developed to address sepsis-induced lung injury (SILI).
Methods: The synthesized nanoparticles were thoroughly characterized to assess their properties.
