A5059430227- Sirtuins and Resveratrol in Medicine
- Computational Drug Discovery Methods
- Calcium signaling and nucleotide metabolism
- Synthesis and biological activity
- Histone Deacetylase Inhibitors Research
- Synthesis and Characterization of Heterocyclic Compounds
- Autophagy in Disease and Therapy
- Synthesis of heterocyclic compounds
- Hepatitis C virus research
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Synthesis and pharmacology of benzodiazepine derivatives
- Cancer Treatment and Pharmacology
- Bioinformatics and Genomic Networks
- Photochromic and Fluorescence Chemistry
- Quinazolinone synthesis and applications
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Synthesis and Reactivity of Heterocycles
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Microbial Natural Products and Biosynthesis
- Pharmacological Receptor Mechanisms and Effects
- HIV/AIDS drug development and treatment
- Toxin Mechanisms and Immunotoxins
- Synthesis and Reactions of Organic Compounds
University of California, Davis
2023-2025
Istanbul University
2010-2024
Biruni University
2018-2023
Martin Luther University Halle-Wittenberg
2014-2019
Université Paris Cité
2018
Sorbonne Paris Cité
2018
Centre National de la Recherche Scientifique
2018
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques
2018
University of Buea
2016
University of Zagreb
1973-2000
Abstract Sirtuins are a highly conserved class of NAD + -dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis cancer, inflammation and neurodegeneration, which makes modulation activity promising strategy for pharmaceutical intervention. A rational basis development optimized inhibitors is lacking so far. Here we present high-resolution structures complex with selective drug-like that show unique inhibitory mechanism. Potency unprecedented selectivity...
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and substrate proteins. Dysregulation human Sirt2 (hSirt2) activity has been associated with pathogenesis cancer, inflammation, neurodegeneration, which makes modulation hSirt2 a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently discovered by us as highly potent isotype-selective inhibitors....
Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in market against cancer until date. Computer-based or silico virtual screening methods are often used lead/hit discovery protocols. In this study, "drug-likeness" ∼400 from African medicinal plants that shown vitro and/or vivo anticancer, cytotoxic, and antiproliferative activities has explored. To verify potential binding to drug targets, interactions between 14 selected targets...
Abstract Sirtuins are NAD + ‐dependent protein deacylases that cleave off acetyl groups, as well other acyl from the ɛ‐amino group of lysines in histones and substrate proteins. Dysregulation human Sirt2 activity has been associated with pathogenesis cancer, inflammation, neurodegeneration, thus making a promising target for pharmaceutical intervention. Here, based on crystal structure complex an optimized sirtuin rearranging ligand (SirReal) shows improved potency, water solubility,...
Controlling the activity of sirtuins is high biomedical relevance as enzymes are involved in cancer, neurodegeneration and other diseases.
Chemical toxins pose a great threat to honey bee health because they affect memory and cognition, diminish immunity, increase susceptibility infection, resulting in decreased colony performance, reproduction, survival. Although the behavioral effects of sub-lethal chemical exposure on bees have been intensively studied, how xenobiotics olfaction, at molecular level, still needs be elucidated. In present work, silico tools, such as docking, binding free energy calculations, dynamics...
Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have generated and validated use virtual screening protocols eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent farnesyltransferase, human glycogen synthase indoleamine 2,3-dioxygenase 1. Pharmacophore were through receiver operating characteristic Güner-Henry scoring methods, indicating that several could...
A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed an l-AP4-derived fragment that mimics and a chain binds into neighboring pocket, offering possibilities to improve affinity selectivity. Herein we describe series of derivatives where the distal replaced aromatic or heteroaromatic group. Potent agonists were identified, including some with mGlu4 subtype preference, e.g., 17m (LSP1-2111) 16g (LSP4-2022)....
HCV is a blood-borne RNA virus that causes acute and chronic hepatitis, cirrhosis, liver failure, hepatocellular carcinoma. In the present work, large in silico combinatorial library was generated using privileged substructures of existing inhibitors NS5B protein. Next, we performed multistep virtual screening process to identify novel inhibitors. Additionally, assessed hit compounds' pharmacokinetic characteristics evaluate their potential as drugs. Hit molecules with drug-like properties...
Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases, which have been linked to the pathogenesis of numerous diseases, including HIV, metabolic disorders, neurodegeneration and cancer. Docking virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted identification two inhibitors sirtuin 1, 2 3 (sirt1–3). Two bichalcones, known as rhuschalcone IV (8) an analogue I (9), previously isolated from medicinal plant Rhus...
Sirtuins are NAD(+)-dependent histone deacetylases (HDACs) that cleave off acetyl but also other acyl groups from the ϵ-amino group of lysines in histones and substrate proteins. Five sirtuin isoforms encoded genome parasitic pathogen Schistosoma mansoni. During its life cycle, S. mansoni undergoes drastic changes phenotype associated with epigenetic modifications. Previous work showed strong effects hSirt2 inhibitors on both worm span reproduction. Thus, we postulate smSirt2 as a new...
The aim of this study was to determine the probable antibacterial, antitubercular, and antiviral activities some N2 -arylidene-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (3a-j). Further structural optimization identified lead structures can us new more active potential agents.Antibacterial title compounds against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa 27853 Escherichia coli 25922. These molecules were also evaluated for their in vitro...
Natural products have been used for the treatment of human diseases since ancient history. Over time, due to lack precise tools and techniques separation, purification, structural elucidation active constituents in natural resources there has a decline financial support efforts characterization products. Advances design chemical compounds understanding their functions is pharmacological importance biomedical field. However, regained attention as sources novel drug candidates upon recent...
Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases and have been linked to the pathogenesis of numerous diseases such as HIV, metabolic disorders, neurodegeneration cancer. Docking virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted identification two inhibitors sirtuin 1, 2 3 (sirt1-3). Two bichalcones; rhuschalcone IV (8) I (9), previously isolated from medicinal plant Rhus pyroides, were shown be active...
Abstract Sirtuine spalten NAD + ‐abhängig Acylreste von Lysinen in Proteinen ab. Eine Fehlregulation humanem Sirt2 wurde mit der Entstehung Krebs, entzündlichen und neurodegenerativen Erkrankungen Verbindung gebracht, was es zu einem vielversprechenden Zielprotein für die Wirkstoffforschung macht. Hier präsentieren wir Entwicklung ersten Sirt2‐selektiven Affinitätssonde auf Basis einer Kristallstruktur Komplex optimierten Hemmstoff aus Klasse SirReals (“Sirtuin Rearranging Ligands”). Dieser...
RNA-dependent RNA polymerase, non-structural protein 5B (NS5B), is an essential enzyme of HCV for viral transcription and genome replication.Its initial validation as a promising target the treatment chronic hepatitis hepatocellular carcinoma has consequently prompted different research institutes pharmaceutical industry to find potential inhibitors human therapies.Among those, anthranilic acid derivatives received increasing attention because their drug-like properties.In order design drug...
Abstract The preparation of substituted N ‐arylisoindolines 3 from simple furan derivatives 1 is reported. Oxatricycloadducts 2, readily accessible by intramolecular Diels‐Alder reaction are susceptible to acidic reagents yielding aromatized products a ring‐opening via intermediate carbocation.
In the imidazo[2,1-b][1,3]thia-zole group of title compound, C(21)H(17)ClN(4)O(2)S, dihedral angle between thia-zole and imidazole rings is 1.9 (2)°. The mean plane this makes angles 5.5 (2) 39.9 (2)° with benzene chloro-phenyl meth-oxy-phenyl groups, respectively. these two 34.4 crystal, mol-ecules are connected to each other by inter-molecular N-H⋯O hydrogen bonds along b axis, generating a C(4) chain. Weak C-H⋯π inter-actions also occur.