One-Pot Synthesis of 1-Thia-4-azaspiro[4.4/5]alkan-3-ones via Schiff Base: Design, Synthesis, and Apoptotic Antiproliferative Properties of Dual EGFR/BRAF^V600E Inhibitors

• Main Authors: Lamya H. Al-Wahaibi (Author), Essmat M. El-Sheref (Author), Mohamed M. Hammouda (Author), Bahaa G. M. Youssif (Author)
• Format: Book
• Published: MDPI AG, 2023-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

In this investigation, novel 4-((quinolin-4-yl)amino)-thia-azaspiro[4.4/5]alkan-3-ones were synthesized via interactions between 4-(2-cyclodenehydrazinyl)quinolin-2(1<i>H</i>)-one and thioglycolic acid catalyzed by thioglycolic acid. We prepared a new family of spiro-thiazolidinone derivatives in a one-step reaction with excellent yields (67-79%). The various NMR, mass spectra, and elemental analyses verified the structures of all the newly obtained compounds. The antiproliferative effects of <b>6a</b>-<b>e</b>, <b>7a</b>, and <b>7b</b> against four cancer cells were investigated. The most effective antiproliferative compounds were <b>6b</b>, <b>6e</b>, and <b>7b</b>. Compounds <b>6b</b> and <b>7b</b> inhibited EGFR with IC₅₀ values of 84 and 78 nM, respectively. Additionally, <b>6b</b> and <b>7b</b> were the most effective inhibitors of BRAF^V600E (IC₅₀ = 108 and 96 nM, respectively) and cancer cell proliferation (GI₅₀ = 35 and 32 nM against four cancer cell lines, respectively). Finally, the apoptosis assay results revealed that compounds <b>6b</b> and <b>7b</b> had dual EGFR/BRAF^V600E inhibitory properties and showed promising antiproliferative and apoptotic activity.

Item Description

10.3390/ph16030467
1424-8247