Anticancer activity of (±)-kusunokinin derivatives as a new HSP90 inhibitor

Background: Cholangiocarcinoma (CCA) is aggressive cancer arising from the malignant transformation of biliary epithelial cells. To date, surgical resection only potential option for CCA patients due to being often chemotherapy-resistant. Therefore, finding a new compound treat necessary. Previously, synthetic (±)-kusunokinin (sKU) and its derivative (bursehernin) represented cytotoxicity effect against well-differentiated (KKU-M213) low on undifferentiated (KKU-K100) Due cytotoxic sKU CCA, modifications chemical were necessary get compound. Material methods: (±)-Kusunokinin derivatives (TTPG1-TTPG5) modified by adding butanol hydroxyl group at 3,4 dimethoxybenzyl butyrolactone part 1,3-benzodioxole part, respectively. Firstly, was evaluated using an MTT assay KKU-M213 KKU-K100 Cell cycle arrest, apoptosis multicaspases activity performed flow cytometry. A molecular docking program used predict target proteins with associated CCA. Target downstream molecules investigated Western blotting. Results: TTPG-5 highest IC50 values 0.01 ± 0.001 μM 1.53 cells, respectively which stronger than sKU. This caused cell arrest G0/G1 phase Moreover, also induced apoptotic cells multi-caspase activity. Using computational prediction protein, bound HSP90-a EC44 (known inhibitor) decreased consequently more suppressed JAK1, STAT3, PI3 K, AKT CyclinB1 Conclusion: exhibited cholangiocarcinoma via suppression induction apoptosis. possible protein TTPG-5. decreased. has ability treatment in future. No conflict interest.