Title:Synthesis, Characterization, Molecular Docking, In Vitro Biological Evaluation and In Vitro Cytotoxicity Study of Novel Thiazolidine-4-One Derivatives as Anti-Breast Cancer Agents
Volume: 21
Issue: 17
Author(s): Zainab Y. Kadhim , Hasanain G.J. Alqaraghuli *Muna Tawfeeq Abd
Affiliation:
- Department of Sciences, College of Basic Education, Al-Muthanna University, Al-Muthanna,Iraq
Keywords:
Thiazolidine-4-one, chemical synthesis, antibacterial activity, anticancer activity, thioglycolic acid, molecular docking.
Abstract:
Background: Thiazolidine-4-one is a promising class of heterocyclic compounds with interesting
pharmacological and biological activities, such as anticancer and antibacterial. Therefore, many researchers have
synthesized thiazolidine-4-ones and evaluated their biological potential for developing new drugs.
Objective: In this study, two novel thiazolidine-4-one derivatives (T1 and T2) were synthesized and evaluated
for their antibacterial activity toward Staphylococcus aureus, Escherichia coli, and Proteus mirabilis. Also, the
cytotoxic activities of compounds T1 and T2 were estimated against MCF-7 (HER2+, ER+, and ER+) and MDAMB-
231 (triple-negative) human breast cancer cell lines. The chemical structures of the compounds T1 and T2
were proven using spectral techniques (FT-IR, 1HNMR, and 13CNMR) and CHN elemental analysis.
Methods: The synthesis of thiazolidine-4-one compounds was performed in two steps. The first step consisted of
the formation of Schiff bases S1 and S2. In the second step, the synthesized Schiff bases were reacted with
thioglycolic acid to prepare thiazolidine-4-one compounds. Hemolysis assay, molecular docking, cytotoxicity
activity (MTT assay), and antibacterial activity (disc diffusion assay) were studied.
Results: The hemolysis study demonstrated that the hemolytic ratio of compounds T1 and T2 at (1, 2, and 3)
mg/ml was less than 4%. MTT assay showed that 100 μg/ml of compounds T1 and T2 diminish the MCF-7 cell
growth up to 80.05 ± 1.72 and 69.85 ± 3.26 respectively after 72hr., while the same concentration of compounds
T1 and T2 reduces the MDA-MB-231 cell growth up 70.28 ± 2.31 and 57.15 ± 1.49, respectively. The inhibition
zones of T1 and T2 were 12 mm at 50 mg/ml and 10 mm at 5 mg/ml in E. coli bacteria. Furthermore, a docking
study was carried out to investigate the affinity and binding mode of compounds T1 and T2 towards the ERα,
VEGF, and HER2 protein receptors in breast cancer cells. Data obtained from the docking study were exactly
identical to that obtained from in vitro cytotoxicity assay.
Conclusion: The results proved that T1 is an optimal anticancer agent toward breast cancer cells and the
hemolysis study indicates the use of safety inside the body for compound T1. Synthesized compound T1 was
most effective against MCF-7 cells compared to MDA-MB-231 cells and more effective than the reference drug
tamoxifen in breast cell lines. The high cytotoxicity of T1 on the growth of MCF‐7 cells because T1 binds with a
high degree of affinity to the estrogen and HER2 receptors, which in turn inhibits cell proliferation and induces
apoptosis.
