A5071321918- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Computational Drug Discovery Methods
- Synthesis and Biological Evaluation
- Metal complexes synthesis and properties
- DNA and Nucleic Acid Chemistry
- Crystallography and molecular interactions
- Click Chemistry and Applications
- Chemical Reaction Mechanisms
- Phenothiazines and Benzothiazines Synthesis and Activities
- Bioactive Compounds and Antitumor Agents
- Protein Kinase Regulation and GTPase Signaling
- Photochemistry and Electron Transfer Studies
- Free Radicals and Antioxidants
- Microbial Natural Products and Biosynthesis
- Biochemical and Molecular Research
- Synthesis and Reactivity of Heterocycles
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- Ferrocene Chemistry and Applications
- Synthesis and bioactivity of alkaloids
- Carbohydrate Chemistry and Synthesis
- Cancer-related Molecular Pathways
Keele University
2019-2025
Bioengineering (Switzerland)
2022
University of Auckland
2012-2021
John Innes Centre
2020
Norwich Research Park
2020
Maurice Wilkins Centre
2016
Institute of Cancer Research
2007-2011
Cancer Research UK
2007-2010
Nottingham Trent University
2007-2009
Max Planck Society
2001-2006
Abstract The theoretical prediction power of the software package QikProp was tested. This achieved by comparing experimentally known results to predicted values. First, simple molecular descriptors for physicochemical properties: octanol–water partition (log P ), water solubility S dipole moment, Ionisation Potential (IP) and Electron Affinity (EA) were compared their determined counterparts. For all descriptors, except EA, a relatively good linear correlation obtained. Experimentally...
The RAPTA pharmacophore was linked to beads identify its biomolecular targets in cancer cells.
Six morpholine-(iso)thiosemicarbazone hybrids HL1-HL6 and their Cu(II) complexes with good-to-moderate solubility stability in water were synthesized characterized. [Cu(L1-6)Cl] (1-6) formed weak dimeric associates the solid state, which did not remain intact solution as evidenced by ESI-MS. The lead proligands displayed higher antiproliferative activity cancer cells than triapine. In addition, 2-5 found to specifically inhibit growth of Gram-positive bacteria Staphylococcus aureus MIC50...
Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and requirement mitochondrial quality control mitophagy for physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal initiated superoxide signaling. Mitophagy was found be mediated PINK1/Parkin-dependent pathway involving p62 as a selective receptor (SAR). Importantly, this...
Oxicams are a versatile family of heterocyclic compounds, and the two representatives meloxicam piroxicam widely used drugs for treatment variety inflammatory rheumatic diseases in humans. As cancer-associated inflammation is known to occur carcinogenesis, we aimed combine compounds carrying bioactive oxicam moieties with ruthenium(arene) fragments, anticancer activity. RuII(arene) complexes methyl ester derivatives scaffold were prepared characterized by standard methods...
The promise of the metal(arene) structure as an anticancer pharmacophore has prompted intensive exploration this chemical space. While N-heterocyclic carbene (NHC) ligands are widely used in catalysis, they have only recently been considered metal complexes for medicinal applications. Surprisingly, a comparatively small number studies reported which NHC ligand was coordinated to RuII(arene) and even less with OsII(arene) pharmacophore. Here, we present systematic study compared symmetrically...
Abstract Ruthenium(II)–arene complexes with biotin‐containing ligands were prepared so that a novel drug delivery system based on tumor‐specific vitamin‐receptor mediated endocytosis could be developed. The characterized by spectroscopic methods and their in vitro anticancer activity cancer cell lines various levels of major biotin receptor (COLO205, HCT116 SW620 cells) was tested comparison the ligands. In all cases, coordination ruthenium resulted significantly enhanced cytotoxicity....
Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors Aurora kinases that possessed 1-benzylpiperazinyl motif at 7-position, and displayed favorable in vitro properties. Cocrystallization Aurora-A with 40c (CCT137444) provided clear understanding into interactions this novel kinases. Subsequent physicochemical property refinement by incorporation solubilizing groups identification...
As ribonucleotide reductase (RNR) plays a crucial role in nucleic acid metabolism, it is an important target for anticancer therapy. The thiosemicarbazone Triapine efficient R2 inhibitor, which has entered ∼20 clinical trials. Thiosemicarbazones are supposed to exert their biological effects through effectively binding transition-metal ions. In this study, six iminodiacetate–thiosemicarbazones able form complexes, as well dicopper(II) were synthesized and fully characterized by analytical,...
Abstract A density functional theory (DFT) study was performed on a collection of clinically approved drugs, or Known Drug Space (KDS), to determine the statistical distribution four properties: dipole moment (DM), polarisability (POL), ionisation potential (IP) and electron affinity (EA). The DM POL are linked cell permeability drugs whereas IP EA reflect their redox stability thus ease metabolism. benchmarking exercise showed good correlation between experimental values predicted...
The development of copper(II) thiosemicarbazone complexes as potential anticancer agents, possessing dual functionality inhibitors R2 ribonucleotide reductase (RNR) and tubulin polymerization by binding at the colchicine site, presents a promising avenue for enhancing therapeutic effectiveness. Herein, we describe syntheses physicochemical characterization four isomeric proligands
Cervical cancer is the fourth leading cause of mortality in women worldwide, with limited therapeutic options for advanced or recurrent cases. In this study, effects a recent thieno[2,3-b]pyridine derivative, (E)-3-amino-5-(3-bromophenyl)acryloyl)-N-(3-chloro-2-methylphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide (compound 1), on two cervical cell lines, HeLa and SiHa, are investigated. Cytotoxicity was assessed by MTT assay, apoptosis rates were measured flow cytometry, metabolic...
To estimate the size of organic chemical space and its sub-regions, i.e. drug-like known drug (KDS).Analysis growth compounds as a function their carbon atoms based on power (f(x)=A×B, C=x) an exponential (f(x)=AeBx). Also, statistical distribution KDS (drugs with good oral-bioavailability) atom count was used to deduce size.The gives superior fit leading 3.4×109 populating space. is predicted be 2.0×106 molecules calculated 1.1×106 compounds.The values here are much smaller than previously...
Abstract High throughput screening (HTS) is extensively used to identify hit and lead compounds in drug discovery programmes. Designing quality libraries a challenge terms of water solubility, stability potential oral bioavailability the compounds. Wines are widely consumed wine inherently soluble, stable relatively non‐toxic. Furthermore, many have been proved health‐beneficial. To evaluate feasibility use 3317 were collected from literature. Their physiochemical properties evaluated with...
The thieno[2,3-<italic>b</italic>]pyridines bind to TDP1 with the best analogue <bold>9d</bold> IC<sub>50</sub> at 0.5 μM.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising therapeutic target in cancer therapy. Combination chemotherapy using Tdp1 inhibitors as component can potentially improve response to many chemotherapeutic regimes. A new set of usnic acid derivatives with hydrazonothiazole pharmacophore moieties were synthesized and evaluated inhibitors. Most these compounds found be potent IC50 values the low nanomolar range. The activity was verified by binding experiments supported molecular modeling....
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current promising inhibition target for the development of new chemosensitizing agents due to its ability remove damage caused by topoisomerase (Top1) poisons such as topotecan irinotecan. Herein, we report our work on synthesis characterization Tdp1 inhibitors that combine arylcoumarin (neoflavonoid) monoterpenoid moieties. Our results showed they are potent with IC50 values submicromolar range. In...