Green and sustainable approaches to Quinazoline-based anticancer agents: Synthesis and structure activity...

Quinazoline derivatives are versatile nitrogen-based heterocycles with strong anticancer potential. Their ability to target biomolecules such as tyrosine kinases, Epidermal Growth Factor Receptor (EGFR), and tubulin makes them important scaffolds in cancer drug design. Conventional synthetic approaches often rely on harsh conditions and toxic reagents, leading to poor atom economy and safety concerns. In contrast, the novelty of this review lies in showcasing how green chemistry principles can be successfully applied to overcome these drawbacks. Environmentally benign methodologies such as microwave-assisted reactions, one-pot synthesis, and the use of green solvents are discussed for the sustainable preparation of quinazoline derivatives. These greener routes not only improve efficiency and yield but also significantly reduce environmental impact, offering a transformative pathway for anticancer drug discovery. Structure-activity relationship (SAR) analyses of green-synthesized quinazoline analogues are summarized to identify key pharmacophoric features responsible for anticancer activity. Among various compounds, 54e exhibited potent cytotoxicity with an IC₅₀ of 1.52 μM against HepG2 cells, while 29f showed strong activity against VERO cells with an IC₅₀ of 3.41 μM. Future directions include using biomass-derived feedstocks, natural catalysts such as rice husk ash and clay, and AI-assisted retrosynthesis for sustainable molecular design. Overall, this review provides a comprehensive insight into eco-friendly synthetic strategies and their impact on the development of potent quinazoline-based anticancer agents.