9Th Brazilian Symposium on Medicinal Chemistry

Mutations in BCR-ABL1 gene are the most studied mechanism of resistance in CML, but fail to explain the cases of resistance. The present study aimed to identify the effect of 5-hydroxy-2-(p-tolylthio)naphthalene-1,4-dione (CNN1) against two CML cell lines. CNN1 showed higher cytotoxicity against multidrug-resistant cell line (FEPs), with IC50 of 0.60 µM, when compared to K562 (IC50=1.12 µM). Imatinib mesylate showed IC50 of 0.10 µM and 10 µM against K562 and FEPs, respectively. Virtual screening predicted topoisomerase 1 (TOP1) as a possible target. Molecular docking simulation predicted a binding affinity of -11,94 kcal/mol between CNN1 and TOP1, via hydrogen bonding to HIS-263, of the active site of the enzyme, and some sites of the DNA strand. To further confirm the results, we performed qPCR and CNN1 suppressed TOP1 gene expression (P<0.05). In summary, CNN1 showed anti-cancer properties suggesting that this compound may be a potential lead drug to new TOP1 inhibitors.