Inhibition of cancer cell invasion by new ((3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide analogs
| Autor: | Ky Youb Nam, Kyoung Tai No, Kyung Hee Song, Seung Youn Jung, Hyun Kyung Choi, Seongho Kho, Jie-Young Song, Seong Mook Kang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Vimentin Biochemistry rab27 GTP-Binding Proteins Exocytosis Extracellular matrix Structure-Activity Relationship 03 medical and health sciences Cell Movement Cell Line Tumor Drug Discovery Humans Molecular Biology Cell Proliferation Extracellular Matrix Proteins Sulfonamides Binding Sites biology Cell growth Chemistry Organic Chemistry Cadherins Protein Structure Tertiary Molecular Docking Simulation Fibronectin 030104 developmental biology rab GTP-Binding Proteins Cell culture Cancer cell biology.protein Molecular Medicine Rab |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:1322-1328 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2015.12.093 |
| Popis: | Rab GTPases regulate various types of intracellular membrane trafficking in all eukaryotes. Since Rab27a and its multiple effectors are involved in exocytosis of lysosome-related organelles and play a major role in malignancy, compounds targeting Rab27a could be likely used to inhibit invasive growth and tumor metastasis. Thus, we designed and synthesized several compounds based on the previously reported Rab27a-targeting synthetic compounds identified by virtual screening, and investigated their anti-metastatic effects in MDA-MB231 and A375 cells. Among the synthesized compounds, (E)-N-(3-chlorophenyl)-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide (3d) and (E)-N-benzyl-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)-N-methylpyridine-3-sulfonamide (3f) significantly inhibited the invasiveness of both tumor cell lines. Compounds 3d and 3f also decreased the levels of signature extracellular matrix marker proteins (fibronectin, collagen, and α-smooth muscle actin) and representative mesenchymal cell markers (N-cadherin and vimentin). Taken together, our results suggest that novel sulfonamide analogs have anti-metastatic activity in breast and melanoma cancer cell lines and may be used as therapeutic agents to treat malignant cancer. |
| Databáze: | OpenAIRE |
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