New pyrimido[5,4-d]pyrimidines with enhanced anticancer activity on colorectal cancer cells: synthesis, SAR study and mechanism of action

Abstract

[Excerpt] Colorectal cancer (CRC) is amongst the most common types of cancer in developed countries due to common sedentary lifestyles and unhealthy diets.1 Chemotherapy has a key role in combating this disease but the current approved drugs are not effective for all patients due to the tumours’ different genetic profiles. The p53 is frequently mutated in several types of cancer causing treatment resistance.2,3,4 Other genetic alterations frequently present in CRC include KRas or BRaf activating mutations which increase proliferative behavior. These mutations are known to be responsible for resistance to targeted therapy with growth factor receptor inhibitor mediated agents. Therefore, the need to increase treatment efficacy and to overcome resistance continues to stimulate anticancer drug discovery. [...]