Design, synthesis and evaluation of new thiazolidin-4-ones as LPA 1 receptor antagonists for breast cancer therapy.
Bhagyalalitha MeduriPavan SrAshwini PrabhuAkshatha Handattu ShankaranarayanaSethu Arun KumarManisha SinghKarthik G PujarGurubasavaraj Veeranna PujarPublished in: Future medicinal chemistry (2024)
Aim: Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)-LPA 1 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 LPA 1 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 LPA 1 protein, LPA 1 and angiogenesis gene expression in treated MCF-7 cells. Molecular docking and molecular dynamic simulation studies reveal the ligand interactions and stability of the LPA 1 -ligand complex. Developed thiazolidin-4-ones showed great potential as an LPA 1 -targeted approach to combating breast cancer.
Keyphrases
- induced apoptosis
- cancer therapy
- endoplasmic reticulum stress
- gene expression
- oxidative stress
- molecular docking
- cell cycle arrest
- signaling pathway
- drug delivery
- breast cancer cells
- endothelial cells
- dna methylation
- cell death
- vascular endothelial growth factor
- molecular dynamics simulations
- pi k akt
- type diabetes
- cardiovascular events
- single cell
- pregnant women
- skeletal muscle
- young adults
- wound healing
- human health