Pharmacological effect of quinazoline-2,4(1H,3H)-dione derivatives: a review

Quinazoline, a nitrogen-containing heterocyclic compound, is widely recognized as a "privileged structure" in the process of drug development. Quinazoline and its derivatives are benzene-pyrimidine fusion compounds that exhibit a broad spectrum of pharmacological properties, including anticarcinogenic, anticonvulsive, and antimicrobial characteristics. Quinazoline-2,4(1H,3H)-dione, an oxidized quinazoline derivative (at positions 2 and 4), possesses a diverse range of pharmacological applications. Quinazoline-2,4(1H,3H)-dione is frequently utilized as a scaffold for synthesizing novel compounds, and recent studies have highlighted its potential in oncotherapy. The derivatives of this compound have been investigated in various types of cancer, such as glioblastoma, osteosarcoma, fibrosarcoma, melanoma, colorectal, prostate, breast, and ovarian cancers. These derivatives have been shown to inhibit critical pathways, such as the Wnt signalling pathway in cancer cells. This review emphasizes the role of quinazoline-2,4(1H,3H)-dione as a versatile scaffold in medicinal chemistry and provides a systematic discussion of its derivatives with a special focus on oncology. We have analyzed structure-activity relationships (SAR), identifying the most promising substitutions at N1, N3, and specific positions on the benzene ring that enhance activity and selectivity. Furthermore, the dual-target inhibition displayed by some derivatives suggests their potential for multi-targeting ability. However, detailed investigations into their broader impact on cancer-related signalling pathways are still limited. The derivatives have also exhibited notable antimicrobial, anticonvulsant, antiinflammatory, antioxidant, antihypertensive, antimalarial, antileishmanial and antidiabetic properties. This study further emphasizes the significance of the quinazoline-2,4(1H,3H)-dione scaffold in drug development.