Indenone derivatives as inhibitor of human DNA dealkylation repair enzyme AlkBH3
| Autor: | Bhavini Kumari, Roy Anindya, Faiz Ahmed Khan, Deepa Akula, Topi Ghosh, Richa Nigam, Subha Narayan Rath, Kaki Raveendra Babu, Prolay Das |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Indenone DNA repair Clinical Biochemistry Biomedical Engineering AlkB Pharmaceutical Science Calorimetry Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Dioxygenase Cell Line Tumor DNA dealkylation Drug Discovery medicine Humans Molecular Biology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry Cancer medicine.disease Molecular Docking Simulation Chemistry 030104 developmental biology Enzyme Indenes chemistry biology.protein Molecular Medicine AlkB Homolog 3 Alpha-Ketoglutarate-Dependent Dioxygenase DNA Biotechnology |
| Zdroj: | Bioorganic & Medicinal Chemistry. 26:4100-4112 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2018.06.040 |
| Popis: | The mammalian AlkB homologue-3 (AlkBH3) is a member of the dioxygenase family of enzymes that in humans is involved in DNA dealkylation repair. Because of its role in promoting tumor cell proliferation and metastasis of cancer, extensive efforts are being directed in developing selective inhibitors for AlkBH3. Here we report synthesis, screening and evaluation of panel of arylated indenone derivatives as new class of inhibitors of AlkBH3 DNA repair activity. An efficient synthesis of 2,3-diaryl indenones from 2,3-dibromo indenones was achieved via Suzuki-Miyaura cross-coupling. Using a robust quantitative assay, we have obtained an AlkBH3 inhibitor that display specific binding and competitive mode of inhibition against DNA substrate. Finally, we established that this compound could prevent the proliferation of lung cancer cell line and enhance sensitivity to DNA damaging alkylating agent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect