# New Derivatives of 4-Piperidinylphenyl-Linked Thiazoles as VEGFR2 Inhibitors with Potential Cytotoxicity Against Renal Cancer

## TL;DR

Researchers developed new thiazole compounds that strongly inhibit VEGFR2 and show promise in fighting renal cancer with better safety than existing drugs.

## Contribution

The study introduces novel thiazole derivatives with potent VEGFR2 inhibition and improved cytotoxicity against renal cancer cells.

## Key findings

- Compounds 7c, 9b, and 9c inhibited VEGFR2 more effectively than sunitinib.
- Compound 7c showed strong cytotoxicity against A498 renal cancer cells with an IC50 of 7.866 µM.
- Compound 7c induced apoptosis and cell cycle arrest in renal cancer cells.

## Abstract

Herein, a novel series of 4-piperidinylphenyl-linked thiazoles was synthesized as VEGFR2 inhibitors with potential cytotoxic activity against renal cancer. Most of the target compounds inhibited VEGFR2 enzyme at sub-micromolar IC50 values. Compounds 7c (IC50 = 0.073 ± 0.002 µM), 9b (IC50 = 0.049 ± 0.002 µM), and 9c (IC50 = 0.093 ± 0.003 µM) were the most potent, showing VEGFR2 inhibition superior to that of sunitinib (IC50 = 0.118 ± 0.003 µM). Furthermore, compounds 7c, 9b, and 9c effectively inhibited the growth of A498 renal cancer cells, with compound 7c being the most potent showing a one-digit IC50 value of 7.866 ± 0.27 µM. In addition, compound 7c revealed a potentially improved safety profile against non-cancerous normal cells, relative to sunitinib. The treatment of A498 renal cancer cells with compound 7c led to an apparent cell cycle arrest and a significant induction of apoptosis. A docking study was also conducted and revealed a proper orientation of compound 7c into the active site of VEGFR2.