A5080155886- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Mast cells and histamine
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Receptor Mechanisms and Effects
- Phenothiazines and Benzothiazines Synthesis and Activities
- Phosphodiesterase function and regulation
- Chemical synthesis and alkaloids
- Click Chemistry and Applications
- Multicomponent Synthesis of Heterocycles
- Neurotransmitter Receptor Influence on Behavior
- Diabetes Treatment and Management
- Neuropeptides and Animal Physiology
Heinrich Heine University Düsseldorf
2021-2024
Universidad de La Laguna
2023
Worcester Polytechnic Institute
2022
Karlsruhe Institute of Technology
2022
University of Coimbra
2022
University of L'Aquila
2022
RISE Research Institutes of Sweden
2022
University of Évora
2022
Georgetown University
2022
In search of new dual-acting histamine H3/sigma-1 receptor ligands, we designed a series compounds structurally based on highly active in vivo ligands previously studied and described by our team. However, kept mind that within the previous series, pair closely related compounds, KSK67 KSK68, differing only piperazine/piperidine moiety structural core showed significantly different affinity at sigma-1 receptors (σ1Rs). Therefore, first focused an in-depth analysis protonation states...
Molecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions highly desirable, since structurally diverse libraries can be attained efficiently an eco-friendly manner. In this work, isatin used as the key building block for Ugi 4-center 3-component reaction synthesis of oxindole–lactam hybrids, under catalyst-free conditions. The resulting oxindole−β-lactam and oxindole−γ-lactam hybrids were evaluated their potential to inhibit relevant central...
Abstract In the last decade, our group has been very active at developing and assaying complex libraries of scaffolds with a focus on their potential to identify bioactive drug candidates for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Attention focused isatin-based oxindole scaffolds, which promising results concerning butyrylcholinesterase (BuChE) inhibitory activity have previously obtained. Considering some published reports detailed analysis pharmacophores...
The oxindole core is an important structural motif in many natural and synthetic substances with various biological activities including anticancer, antineurodegenerative, antimicrobial properties. This report focuses on the synthesis activity of a series novel N-substituted 3-aminooxindoles their assessment cholinesterase (ChE) monoamine oxidase (MAO) inhibition. With regard to MAO inhibition, N-propargyl containing derivatives was synthesized screened. Despite being weak inhibitors MAO-A...
A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened in vitro for inhibition deoxyribonuclease I (DNase I). Compounds 22, 8 7 are among the most potent synthetic non-peptide DNase reported to date. Three 8-hydroxyquinoline analogues inhibited both BChE with IC50 values below 35 μM 50 nM, respectively, while two nitroxoline derivatives Cat endopeptidase activity 60 20 μM. Selected were various co-target binding affinities at dopamine D2 D3 , histamine H3...
Continuing with our program to obtain new histamine H3 receptor (H3R) ligands, in this work we present the synthesis, H3R affinity and silico studies of a series eight synthetically accessible purine derivatives. These compounds are designed from isosteric replacement scaffold presented previous ligand, pyrrolo[2,3-d]pyrimidine ring, by core. This design also considers maintaining fragment bipiperidine at C-4 aromatic rings electron-withdrawing groups N-9, as these fragments part proposed...
Abstract Bis(benzimidazol‐2‐yl)amine scaffold is not present in dipeptidyl peptidase‐4 (DPP‐4) inhibitors published so far. Herein, the inhibitory potential of bis(benzimidazol‐2‐yl)amine derivatives against DPP‐4 was evaluated. In non‐competitive inhibition mode, three representatives 5 , 6 and 7 inhibited vitro with IC 50 values below μM. The assessed binding pocket for these benzimidazoles includes S2 extensive subsite's residues Phe357 Arg358. None lead compounds showed cytotoxicity to...
Abstract Dopamine D 2 ‐like receptors, especially and 3 receptor subtypes, are important targets of antipsychotic agents. Many these antipsychotics share an aliphatic linker element between a protonable amine group acyl‐like moiety. Here, we have modified this into phenylmethyl phenylethyl linkers substituted in different positions. The design, synthesis, vitro evaluation 18 dopamine ligands were performed study. Using radioligand displacement assay, all found to modest nanomolar affinity R...