Synthesis, characterization, molecular docking and in vitro anti-cancer activity studies of new and highly selective 1,2,3-triazole substituted 4-hydroxybenzohyrdazide derivatives

ŞENOL H., Ağgül A. G., ATASOY S., Güzeldemirci N. U.

Journal of Molecular Structure, vol.1283, 2023 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1283
  • Publication Date: 2023
  • Doi Number: 10.1016/j.molstruc.2023.135247
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: 1,2,3-triazole, Arylidenehydrazide, Breast cancer, Cytotoxicity, HER2, Molecular docking, Thiazolidin-4-one
  • Istanbul University Affiliated: Yes


In this study, 16 new hybrid compounds 6(a-h) and 7(a-h) were synthesized starting from methylparaben. These new compounds consist of eight 1,2,3-triazole-arylidenehydrazide derivatives and eight 1,2,3-triazole-thiazolidin-4-one derivatives. All compounds were tested against MCF-7 breast cancer cells and MCF10A breast healthy tissue to determine their anti-cancer activity. Molecular docking studies were also carried out against receptor proteins (HER2, EGFR, and VEGFR1) that are related to the growth factor of cancer cells to understand the inhibition mechanism. According to the results of in silico and in vitro activity studies, compounds 6g and 7g were found as the highest selective and active against breast cancer cells. The IC50 values of compounds 6g and 7g against MCF7 cells were found as 8.48 and 4.38 µM, respectively. In addition, the IC50 values of compounds 6g and 7g against MCF10A cells were found as 114.80 and 170.60 µM. When comparing the selectivity of the 6g and 7g to the reference drug doxorubicin, 6g and 7g had higher selectivity (13.5 and 39 respectively) compared to doxorubicin (4). The compound 7g also showed activity against cancer cells at lower doses and was found to be safe against healthy cells at high doses. Molecular docking results showed that both 6g and 7g had higher binding scores for all 3 target enzymes and especially for HER2 protein related to breast cancer with binding scores of -8.059 kcal and -9,008 kcal respectively, while doxorubicin had a binding score of -7.854 kcal. According to the results of the in vitro, and in silico study, compound 7g which was synthesized in this study is a promising, potent, and selective anti-cancer drug candidate for the treatment of breast cancer. All the tested compounds were very well characterized by spectroscopic methods and they have at least 95% HPLC purity.