Design, synthesis and evaluation of new thiazolidin-4-ones as LPA 1 receptor antagonists for breast cancer therapy

Aim: Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)–LPA₁ pathway using small molecules could improve breast cancer therapy. Materials & methods: Thiazolidin-4-ones were developed and tested on MCF-7 cancer cells, and active compounds were analyzed for their effects on apoptosis, migration angiogenesis and LPA₁ protein and gene expression. Results & conclusion: Compounds TZ-4 and TZ-6 effectively reduced the migration of MCF-7 cells, and induced apoptosis. TZ-4, TZ-6, TZ-8 and TZ-14 significantly reduced the LPA₁ protein, LPA₁ and angiogenesis gene expression in treated MCF-7 cells. Molecular docking and molecular dynamic simulation studies reveal the ligand interactions and stability of the LPA₁–ligand complex. Developed thiazolidin-4-ones showed great potential as an LPA₁-targeted approach to combating breast cancer. Breast cancer is a major cause of death for women worldwide. Using small molecules to target the lysophosphatidic acid (LPA)–LPA₁ pathway could improve breast cancer treatment. We tested a type of molecule called thiazolidin-4-ones on breast cancer cells in the lab. We looked at how these molecules affected cell death, movement, blood vessel growth and the activity of the LPA₁ gene and protein. Some of these molecules, such as TZ-4 and TZ-6, reduced the movement of cancer cells and caused them to die. They also decreased the levels of LPA₁ protein and gene activity in the cells. We used computer simulations to see how these molecules interacted with the LPA₁ protein. Our findings suggest that thiazolidin-4-ones could be a promising treatment for breast cancer by targeting LPA₁. New thiazolidin-4-ones were tested on MCF-7 cells; active compounds were analyzed for effects on apoptosis, migration, angiogenesis and LPA₁ expression. TZ-4 and TZ-6 reduced MCF-7 migration and induced apoptosis. Novel thiazolidin-4-ones as LPA₁ inhibitors and their subsequent effects. The study focused on developing novel thiazolidin-4-one based lysophosphatidic acid receptor-1 (LPA₁) inhibitors to target breast cancer. Compounds TZ-4, TZ-6, TZ-8 and TZ-14 reduced LPA₁ expression and were most effective against MCF-7 breast cancer cells, with low toxicity. All the designed molecules showed potential and stable interactions for amino acids of LPA₁ binding pocket with less binding energy compared to the co-crystal structure. The compounds TZ-4, TZ-6, TZ-8 and TZ-14 show promise as potential candidates for breast cancer therapy with a focus on LPA₁ modulation.