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Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities
- Source :
- European Journal of Medicinal Chemistry. 157:1068-1080
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Vinyl sulfone or sulfoxide moieties were firstly introduced to the structure of chalcone compound by replacing the carbonyl group to afford a series of novel compounds as potential anti-tubulin agents. All of the target compounds were evaluated for their anti-proliferative activity. Among them, compound 12m showed the most potent activity against a panel of cancer cell lines with IC50 values ranging from 0.128 to 0.606 μM. Further mechanism studies demonstrated that compound 12m caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Moreover, compound 12m reduced the cell migration and disrupted the capillary-like tube formation in human umbilical vein endothelial cell (HUVEC) assays. Importantly, compound 12m significantly and dose dependently inhibited tumor growth in H22 liver cancer allograft mouse model, which is more potent than control compound CA-4, suggesting that 12m deserves further research as a potential anti-tubulin agent targeting colchicine binding site on tubulin.
- Subjects :
- Models, Molecular
0301 basic medicine
Chalcone
Antineoplastic Agents
Apoptosis
Microtubules
01 natural sciences
Polymerization
Microtubule polymerization
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Cell Movement
Cell Line, Tumor
Drug Discovery
Human Umbilical Vein Endothelial Cells
Humans
Sulfones
Cell Proliferation
Pharmacology
Tube formation
Wound Healing
Dose-Response Relationship, Drug
Molecular Structure
biology
010405 organic chemistry
Organic Chemistry
Cell migration
Sulfoxide
Neoplasms, Experimental
General Medicine
0104 chemical sciences
030104 developmental biology
Tubulin
chemistry
Biochemistry
biology.protein
Human umbilical vein endothelial cell
Drug Screening Assays, Antitumor
Intracellular
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....480c8f60d173a81ea8ac287970c9ac39