Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase

• Main Authors: Malose Jack Mphahlele (Author), Hugues K. Paumo (Author), Yee Siew Choong (Author)
• Format: Book
• Published: MDPI AG, 2017-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1424-8247; 10.3390/ph10040087
• Keywords: 6-bromo-4-chloroquinazolines; amination; Suzuki-Miyaura cross-coupling; cytotoxicity; EGFR-TK; molecular docking; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 10, Iss 4, p 87 (2017)

Series of the 2-unsubstituted and 2-(4-chlorophenyl)-substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)-substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR molecular docking model suggested that these compounds are nicely bound to the region of EGFR.