A5029259484- Computational Drug Discovery Methods
- Synthesis and biological activity
- Analytical Chemistry and Chromatography
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- Tuberculosis Research and Epidemiology
- Bioactive Compounds and Antitumor Agents
- Mycobacterium research and diagnosis
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Malaria Research and Control
- Research on Leishmaniasis Studies
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Crystallization and Solubility Studies
- Cholinesterase and Neurodegenerative Diseases
- Antibiotic Resistance in Bacteria
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Synthesis and Characterization of Heterocyclic Compounds
- Quinazolinone synthesis and applications
- HIV/AIDS drug development and treatment
- Phenothiazines and Benzothiazines Synthesis and Activities
- Genomics, phytochemicals, and oxidative stress
- Protein Kinase Regulation and GTPase Signaling
National University of Singapore
2016-2025
Kyonggi University
2025
Agency for Science, Technology and Research
2021
Bioinformatics Institute
2021
Singapore Eye Research Institute
2021
Tsinghua University
2010
Sichuan University
2010
Osaka University of Pharmaceutical Sciences
2003
Mahidol University
2001
University of Catania
1996
Chalcones with 2',3',4'-trimethoxy, 2',4'-dimethoxy, 4'-methoxy, 4'-ethoxy, 2',4'-dihydroxy, and 4'-hydroxy groups on ring B were synthesized evaluated in vitro against Plasmodium falciparum (K1) a [3H] hypoxanthine uptake assay. The other A was quinoline, pyridine, naphthalene, or phenyl rings electron-donating electron-withdrawing substituents of varying lipophilicities. Trimethoxy 6 27, dimethoxy 7, 8, 29, methoxy 31 analogues had good activities (IC50 < 5 μM). 3-Quinolinyl derivatives...
New drugs against tuberculosis are urgently needed. The tryptophan (Trp) analog indole propionic acid (IPA) is the first antitubercular metabolite produced by human gut bacteria. Here, we show that this antibiotic blocks Trp synthesis, an in vivo essential biosynthetic pathway M. . Intriguingly, IPA acts decoupling a bacterial feedback regulatory mechanism: it mimics as allosteric inhibitor of anthranilate synthase, thereby switching off synthesis regardless intracellular levels....
A number of proteins involved in cell growth control, including members the Ras family GTPases, are modified at their C terminus by a three-step posttranslational process termed prenylation. The enzyme isoprenylcysteine carboxylmethyl-transferase (Icmt) catalyzes last step this process, and genetic pharmacological suppression Icmt activity significantly impacts on oncogenesis. Screening diverse chemical library led to identification specific small molecule inhibitor Icmt, cysmethynil, that...
Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay emergence of resistance. Here we report antimycobacterial activities 4-fluoro 6-methoxyindoles bearing a cationic amphiphilic motif represented by lipophilic n-octyl side chain at position 1 positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety 3. These analogues exhibited balanced profiles potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective...
Persistence of infection despite extensive chemotherapy with antibiotics displaying low MICs is a hallmark lung disease caused by Mycobacterium abscessus (Mab). Thus, the classical MIC assay poor predictor clinical outcome. Discovery more efficacious requires predictive in vitro potency assays. As mycobacterium, Mab an obligate aerobe and chemo-organo-heterotroph - it oxygen organic carbon sources for growth. However, bacteria growing patients can encounter micro-environmental conditions...
A series of alkoxylated and hydroxylated chalcones previously reported to have antiplasmodial activities in vitro were investigated for their effects on the new permeation pathways induced by malaria parasite host erythrocyte membrane. Of 21 compounds with good (50% inhibitory concentrations [IC(50)s], < or = 20 microM), 8 members found inhibit sorbitol-induced lysis parasitized erythrocytes a significant extent (< 40% control values) at concentration (10 microM) that was close IC(50)s....
Inhibitors of isoprenylcysteine carboxylmethyltransferase (Icmt) are promising anti-cancer agents, as modification by Icmt is an essential component the protein prenylation pathway for a group proteins that includes Ras GTPases. Cysmethynil, prototypical indole-based inhibitor Icmt, effectively inhibits tumor cell growth. However, physical properties cysmethynil, such its low aqueous solubility, make it poor candidate clinical development. A novel amino-derivative cysmethynil with superior...
Although the mechanisms and susceptibility factors of troglitazone-associated idiosyncratic liver injury have not been elucidated, experimental evidence has identified oxidant stress mitochondrial as a potential hazard in vitro. In search upstream mediators toxicity, we hypothesized that troglitazone-induced increased generation superoxide might activate thioredoxin-2 (Trx2)/apoptosis signal–regulating kinase 1 (Ask1) signaling pathway, leading to cell death, that, hence, mitochondrially...
Multitarget agents have been increasingly explored for enhancing efficacy and reducing countertarget activities toxicities. Efficient virtual screening (VS) tools searching selective multitarget are desired. Combinatorial support vector machines (C-SVM) were tested as VS dual-inhibitors of 11 combinations 9 anticancer kinase targets (EGFR, VEGFR, PDGFR, Src, FGFR, Lck, CDK1, CDK2, GSK3). C-SVM trained on 233−1,316 non-dual-inhibitors correctly identified 26.8%−57.3% (majority >36%) the...
Abstract The ability of aurones to modulate the efflux activities ABCG2 and ABCB1 was investigated by quantifying their effects on accumulation pheophorbide A (PhA) in ABCG2‐overexpressing MDA‐MB‐231/R cells calcein AM ABCB1‐overexpressing MDCKII/MDR1 cells. Key structural features for interactions at both are a methoxylated ring A, an intact exocyclic double bond, location carbonyl bond C. Modifications rings B C were less critical served primarily moderate activity selectivity one or...