Review: synthesis and anticancer activity of pyrimido4,5-bquinolines in the last twenty years

Abstract Pyrimido4,5- b quinoline is a vital structural motif. The synthesis of pyrimido4,5- b quinolines has been a challenging topic in medicinal chemistry. A wide range of starting materials have been employed to achieve this nucleus such as quinoline derivatives and isatins. Multi-component one-pot synthestic approaches were employed either by using barbituric or thiobarbituric acid, amines and aldehydes or from 6-aminouracils, aldehydes and cyclohexanone derivatives. Recent synthetic strategies and many green chemistry techniques have improved pyrimido4,5- b quinolines synthesis over the last twenty years. Among the many reported biological activities of pyrimido4,5- b quinolines, anticancer activity attracted research attention over the past couple of decades. Many derivatives have shown promising anticancer activity on different cancer cell lines such as MCF-7, A549, K562 and others. They also demonstrated activity on different enzymes and receptors such as tyrosine kinases, tyrosyl-DNA Phosphodiesterase II and HDM2 ubiquitin ligase (E3) that promote apoptosis, repair DNA damage, and induce cell cycle arrest. This review critically examines the recent synthetic approaches employed for the synthesis of pyrimido4,5- b quinolines and explores their reported anticancer activities.