Synthesis, antiproliferative activity, molecular docking studies of hydrazone functionalised thioparabanic acid and rhodanine analogues

Abstract

Twenty new samples of hydrazone functionalized thioparabanic acid and rhodanine analogues were prepared by reacting a mixture of acyl methylene substituted rhodanine and hydantoin compounds with hydrazine and acyl hydrazine derivatives in good yields (53–89%). The cytotoxic effect of newly synthesized compounds 3a–g, 4a–m was evaluated on the human colon cancer cell line (DLD-1) and human liver cancer cell line (HepG2) by comparison with cisplatin as a positive control drug. Two of the molecules (3f [2-hydroxy-N'-((Z)-1-(5-oxo-2-thioxoimidazolidin-4-ylidene)propan-2-ylidene)benzohydrazide], 3g [(5Z)-5-(2-(2-(3,4-dimethylphenyl)hydrazono)propylidene)-2-thioxoimidazolidin-4-one]) showed significant inhibition on cancer cells. Particularly, one of the molecules (3f) was found to be more effective than cisplatine with IC₅₀ values of 4.71 µM and 2.79 µM for DLD-1, HepG2, respectively. Selectivity of the most active five compounds was screened against a healthy human cell line (Wl-38). Compounds 3g and 4l, which are, respectively, thioparabanic acid and rhodanine derivatives, demonstrated good selectivity, and it was observed that the toxic effect of these compounds was more on colon and liver cancer cells than on normal lung cells. The molecular docking evaluations for active 3f and 3g molecules on the liver and colon cancer were conducted to support the obtained experimental results with the in silico AutoDock Vina program and the results were shown to support each other.

Graphical Abstract

Keywords:

• Antiproliferative activity
• molecular docking
• thioparabanic acids
• rhodanine analogues
• hydrazone

Acknowledgment

Author would like to thank Prof. Dr. Fatih Ucun for his helpful contribution and Gaussian Calculations.

Author’s contributions

ŞHÜ, ÜÇ, and İEK performed the chemistry experiment and molecular characterizations. SA performed the biological activity experiments. YS performed molecular docking study. All authors discussed the results and commented on the manuscript.

Conflicts of interest

There are no conflicts of interest to declare.

Additional information

Funding

This study was supported by the Science and Technology Practice & Research Center of Yozgat Bozok University, Turkey (Project No: 2015FBE/T198). SA would like to thank Suleyman Demirel University Research Fund for financial support with project number TSG-2021-8458.