A5068331833- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Enzyme function and inhibition
- Synthesis and biological activity
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Heat shock proteins research
- Multiple Myeloma Research and Treatments
- Cancer therapeutics and mechanisms
- Glioma Diagnosis and Treatment
- Cholinesterase and Neurodegenerative Diseases
- Cancer Mechanisms and Therapy
- Estrogen and related hormone effects
- Veterinary medicine and infectious diseases
- Beetle Biology and Toxicology Studies
- Toxin Mechanisms and Immunotoxins
- ATP Synthase and ATPases Research
- Retinoids in leukemia and cellular processes
- Retinal Diseases and Treatments
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Cancer-related Molecular Pathways
- Alkaloids: synthesis and pharmacology
- Pancreatic and Hepatic Oncology Research
Taipei Medical University
2013-2025
A series of bicyclic arylamino/heteroarylamino hydroxamic acids (7–31) have been examined as novel histone deacetylase 6 (HDAC6) inhibitors. One compound (13) exhibits remarkable inhibitory activity HDAC6 with an IC50 value 0.29 nM, which is 4,000–43,000 times more selective over other HDAC isoforms. Compound 13 was shown to antiproliferative against human multiple myeloma RPMI 8226, U266, and NCI-H929 cells no effect on normal bone marrow cells. 13, a single drug, suppresses the growth...
This paper reports the development of a series 5-aroylindolyl-substituted hydroxamic acids. N-Hydroxy-4-((5-(4-methoxybenzoyl)-1H-indol-1-yl)methyl)benzamide (6) has potent inhibitory selectivity against histone deacetylase 6 (HDAC6) with an IC50 value 3.92 nM. It decreases not only level phosphorylation tau proteins but also aggregation proteins. Compound shows neuroprotective activity by triggering ubiquitination. In animal models, compound is able to ameliorate impaired learning and...
Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood–brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery. The results indicated histone deacetylase modification, referred as compound 1, demonstrated promising cytotoxic...
A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI50 values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, 6 isoenzymes inhibitory IC50 12.3, 4.0, 1.0 nM, respectively, which are comparable 1. In in vivo efficacy evaluation...
Preliminary biological data on 7-anilino-6-azaindoles (8–11) suggested that hydrophobic substituents at C7 contribute to enhancement of antiproliferative activity. A novel series 7-aryl-6-azaindole-1-benzenesulfonamides (12–22) were developed and showed improved cytotoxicity compared ABT751 (5). The conversion phenyl rings into heterocycles led a remarkable improvement Among all the synthetic products, 7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole (21) exhibited most potent...
Oncogenic K-Ras signaling highly relies on the canonical Ras/MEK/ERK pathway to contribute pancreatic cancer progression. However, numerous efforts of MEK inhibitors have failed provide an optimal antitumor effect for in practice. The aim present work was develop a more efficacious therapeutic intervention through combination with histone deacetylase (HDAC) inhibitor MPT0E028.The effects combined therapy cell viability, apoptosis, protein, and RNA expressions were determined by MTT assay,...
Recently, histone deacetylase (HDAC) inhibitors have emerged as a promising class of drugs for treatment cancers, especially subcutaneous T-cell lymphoma. In this study, we demonstrated that MPT0E028, novel N-hydroxyacrylamide-derived HDAC inhibitor, inhibited human colorectal cancer HCT116 cell growth in vitro and vivo. The results NCI-60 screening showed MPT0E028 proliferation both solid hematological tumor lines at micromolar concentrations, was potent cells. had stronger apoptotic...
A series of 7-arylindoline-1-benzenesulfonamides were prepared and evaluated for anticancer activity. 7-(4′-Cyanophenyl)indoline-1-benzenesulfonamide 15 exhibited substantial antiproliferative activity with IC50 values ranging from 17–32 nM against a variety human cancer cell lines, including MDR resistant line. Compound (IC50 = 1.5 μM) also showed more potent inhibition tubulin polymerization than 4a (combretastatin A-4, 2.0 displayed strong binding to the colchicine site tubulin.
In an attempt to mimic the 3,4,5-trimethoxyphenyl-Z-stilbene moiety of combretastatin A-4, a series N-aryl-5,6,7-trimethoxyindoles were synthesized via copper-catalyzed Ullmann-type N-arylation through corresponding 5,6,7-trimethoxyindole and aryl halides. These compounds demonstrated potent antiproliferative activity providing novel skeleton for tubulin polymerization inhibitors.
A series of 3-subsituted quinolinehydroxamic acids has been synthesised and evaluated for their effect on human lung cancer cell line (A549), colorectal (HCT116) HDAC isoforms 1, 2, 6, 8. The results indicated that substitution at C3 quinoline is favoured HDAC6 selectivity. Two compounds (25 26) were also found to be potent anti-proliferative with IC50 values ranging from 1.29 2.13 µM against A549 HCT116 cells. These displayed remarkable selectivity over other nanomolar values. Western blot...
Despite great advances in the treatment of acute leukemia, a renaissance current chemotherapy needs to be improved. The present study elucidates underlying mechanism new synthetic quinoline derivative, MPT0B392 (B392) against leukemia and its potential anticancer effect drug resistant cells. B392 caused mitotic arrest ultimately led apoptosis. It was further demonstrated novel microtubule-depolymerizing agent. effects oral administration showed relative potent anti-leukemia activity an vivo...