Design, Synthesis, Molecular Docking, Dynamics Simulation, and Biological Evaluation of Novel Thiazolidinedione Derivatives Against Breast Cancer with Apoptosis-Inducing Activity
Abstract
Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. The chemotherapeutic drugs used in treatment often have serious side effects. In light of their anticancer potential, thiazolidinedione (TZD) derivatives are considered to be promising candidates for the development of novel antitumor agents. The objective of this study is to synthesize and produce two sets of TZD derivatives by combining the structural features of microtubule-targeting drugs used in breast cancer treatment, and to determine their molecular docking, molecular dynamics simulations, ADMET profile, antiproliferative, and apoptotic effect potential. In the present study, PZ-11 was determined by xCELLigence analysis to have the highest antiproliferative potential among all compounds tested on MCF-7 breast cancer cells. The cytotoxic activity of the synthesized compounds was evaluated against MCF-7 breast cancer cells, revealing IC50 values of 29.44 μM for PZ-9 and 17.35 μM for PZ-11, compared to 6.45 μM for the reference drug vincristine. Analysis of the gene expression of the PZ-11 compound, which has a stronger cytotoxic effect potential, showed that PZ-11 significantly downregulates AIFM1, BAG3, and BIRC3, while upregulating pro-apoptotic genes such as BAD, HRK, CASP10, and CASP14. PZ-11's binding affinities were screened using a molecular docking workflow via KNIME. The robust and persistent interactions between PZ-11 and AIF were substantiated by molecular…
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Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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