The effect of novel hydrazone derivatives on human brain, triple–negative breast, and skin cancer cell lines

Triple–negative breast cancer accounts for 10–15% of all new cases of breast cancer but has a poor prognosis and aggressive behavior [1]. Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US [2]. The global incidence of glioblastoma is considered rare but with poor prognosis and a survival rate of 14–15 months [3]. Targeted drugs have made remarkable progress in the treatment of cancer. Therefore, potential kinase inhibitor hydrazone derivatives are expected to contribute to the efficacy of treatment. The aim of our research was to evaluate the anticancer activity of hydrazone derivatives synthesized at Kaunas University of Technology (Lithuania) in human triple–negative breast, melanoma, and glioblastoma cell lines. In our study, we investigated the activity of 22 hydrazone derivatives bearing substituted aromatic and different heterocyclic moieties on triple–negative breast cancer cell line MDA–MB231, melanoma cell line IGR39, and glioblastoma cell line U87. The effect on cell viability was determined by the MTT assay at 50 μM of compounds after 72 hours of incubation. Compounds with significant cell viability–reducing capabilities were chosen for further studies and the EC50 values were established. Compounds IT199, IT207, IT224, IT227, and IT231 reduced the viability of at least one cell line by up to appr. 20–25%. Evaluation of the selectivity of the compounds for cancer cells showed that compound IT224 is selective to IGR39 and IT231 is selective to MDA–MB231 cell line, compound IT199 is selective to IGR39 and MDA–MB231 and IT207 is selective to IGR39 and U87 cell lines while the compound IT227 significantly reduced all three cell lines investigated in this study. These compounds were selected for the determination of EC50 values, which would be used for further studies on cell migration and the activity on 3D cell cultures. Based on estimated EC50 values, IT207 and IT227 reduced the viability of IGR39 cell line about 50% stronger than sunitinib. Compound IT227 reduced the viability of MDA–MB231 cell line 2 times stronger than sunitinib. Compounds IT199, IT207 and IT227 reduced the viability of U87 cell line from 3 to 9 times. In conclusion, compounds IT199, IT207, IT224, IT227, and IT231 showed a significant reduction of cell viability by MTT assay and were chosen as potent candidates for further anticancer activity studies.