A5068845562- Redox biology and oxidative stress
- Genomics, phytochemicals, and oxidative stress
- Rheumatoid Arthritis Research and Therapies
- Spondyloarthritis Studies and Treatments
- Synthesis and Biological Evaluation
- Glutathione Transferases and Polymorphisms
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Medication Adherence and Compliance
- Synthesis and biological activity
- Cancer-related Molecular Pathways
- Bipolar Disorder and Treatment
- Probiotics and Fermented Foods
- Metal complexes synthesis and properties
- Psoriasis: Treatment and Pathogenesis
- Sulfur Compounds in Biology
- Natural product bioactivities and synthesis
- Sesquiterpenes and Asteraceae Studies
- Phytochemistry and Biological Activities
- Autophagy in Disease and Therapy
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- IL-33, ST2, and ILC Pathways
- Hepatitis C virus research
- Toxoplasma gondii Research Studies
National University of Singapore
2015-2024
University College London
2014
Nobel Foundation
2007-2008
Karolinska Institutet
2007-2008
NIHR Nottingham Digestive Diseases Biomedical Research Unit
2006-2007
University of Nottingham
2004-2007
Scripps Research Institute
2007
Queen's Medical Centre
2006
Cancer Research UK
2004
Max Delbrück Center
2004
Arsenic trioxide (ATO) is an effective cancer therapeutic drug for acute promyelocytic leukemia and has potential anticancer activity against a wide range of solid tumors. ATO exerts its effect mainly through elevated oxidative stress, but the exact molecular mechanism remains elusive. The thioredoxin (Trx) system comprising NADPH, reductase (TrxR), Trx glutathione (GSH) composed reductase, GSH supported by glutaredoxin are two electron donor systems that control cellular proliferation,...
Mercury toxicity mediated by different forms of mercury is a major health problem; however, the molecular mechanisms underlying remain elusive. We analyzed effects mercuric chloride (HgCl(2)) and monomethylmercury (MeHg) on proteins mammalian thioredoxin system, reductase (TrxR) (Trx), glutaredoxin glutathione (GR) (Grx). HgCl(2) MeHg inhibited recombinant rat TrxR with IC(50) values 7.2 19.7 nm, respectively. Fully reduced human Trx1 bound lost all five free thiols activity after incubation...
Aims: The role of thioredoxin reductase (TrxR) in tumorigenesis has made it an attractive anticancer target. A systematic approach for development novel compounds as TrxR inhibitors is currently lacking. Structurally diversified share common electrophilic propensities the sulfhydryl groups, among which include Michael reaction acceptors containing α,β-unsaturated carbonyl moiety. We aimed to identify features structurally acceptor-based that would yield a strong inhibitory character....
Cullin-based E3 ligases are a large family of multi-subunit ubiquitin with diverse cellular functions, including the regulation cell cycle, DNA damage response, and various transcription factors. These composed one six mammalian cullin homologs (Cul1, Cul2, Cul3, Cul4a, Cul4b, Cul5), Ring finger containing protein Roc1/Rbx1, homolog-specific adaptor substrate recognition subunits. To be active, cullin-based require covalent modification conserved lysine residue in ubiquitin-like Nedd8. We...
The dihydrofolate reductase (DHFR) and thioredoxin (TrxR) enzymes are involved in the process of tumor cell growth survival. 4,6-diamino-1,2-dihydro-1,3,5-triazine scaffold is well-established as a useful for DHFR inhibition, while chalcones have been reported to be inhibitors TrxR. In this study, 15 novel compounds designed by structural combination chalcone scaffolds via diether linker were successfully synthesized characterized. All demonstrated dual inhibition against TrxR when they...
Abstract Heteroaromatic quinols 4-(benzothiazol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1) and 4-(1-benzenesulfonyl-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (2) exhibit potent selective antitumor activity against colon, renal, breast carcinoma cell lines in vitro (GI50 < 500 nmol/L). In vivo growth inhibition of xenografts has been observed. Profound G2-M cycle block accompanied down-regulation cdk1 gene transcription was corroborated by decreased CDK1 protein expression following...
Hypoxia-inducible factor (HIF) is a heterodimeric transcription that composed of hypoxia-inducible α subunit (HIF-1α and HIF-2α) constitutively expressed β (HIF-1β). HIF mediates the adaptation cells tissues to low oxygen concentrations. It also plays an important role in tumorigenesis constitutes therapeutic target anti-tumor therapy. We have screened number reported inhibitors for their effects on HIF-transcriptional activity found DNA damage inducing agents camptothecin mitomycin C...
Novel heteroaromatic-substituted 4-hydroxycyclohexa-2,5-dienones (quinols) demonstrate potent in vitro antiproliferative activity and vivo antitumor tumor xenografts. The mechanism of action these promising novel anticancer agents, however, remains to be fully elucidated. thioredoxin (Trx) system comprising Trx, reductase (TrxR), NADPH participates a broad range cellular functions involved cell survival proliferation. Accumulating evidence has indicated that the selenocysteine-containing...
A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones (indolylquinols) has been synthesized on the basis discovery lead compound 1a and screened for antitumor activity. Synthesis this novel was accomplished via "one-pot" addition lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise related naphtho-, 1H-indole-, benzimidazole-substituted quinols. number compounds...
Multifunctional trans-cinnamaldehyde (CA) and its analogs display anti-cancer properties, with 2-benzoyloxycinnamaldehyde (BCA) 5-fluoro-2-hydroxycinnamaldehyde (FHCA) being identified as the ortho-substituted that possess potent anti-tumor activities. In this study, BCA, FHCA a novel analog 5-fluoro-2-benzoyloxycinnamaldehyde (FBCA), were demonstrated to decrease growth colony formation of human colon-derived HCT 116 mammary-derived MCF-7 carcinoma cells under non-adhesive conditions. The...
Several compounds bearing the indolinone chemical scaffold are known to possess anticancer properties. For example, tyrosine kinase inhibitor sunitinib is an arylideneindolin-2-one compound. The versatility associated with structural modifications of underlies potential discover additional derivatives possessing Previously synthesized 3-(2-oxoethylidene)indolin-2-one compounds, also as supercinnamaldehyde (SCA) in reference parent compound 1 [1-methyl-3(2-oxopropylidene)indolin-2-one], bear...