Triazolo pyrimidine derivatives of coumarin and benzocoumarin: green synthesis, biological activity screening study with in silico evaluation

In the current study, triazolo pyrimidine coumarin and benzocoumarin derivatives were prepared using green methods as a fast and cost-efficient strategy in comparison with the traditional method in terms of reaction time and yield. Combining coumarins with other bioactive compounds could improve the anticancer properties and other biological activities. Therefore, both compounds were evaluated in silico as potential early-stage small molecule inhibitors of three targets, which cause four life-threatening diseases: leukaemia FLT3 (PDB: 4XUF), SARS-COV-2 (3CLpro) (PDB: 6M2N), and adenosine A1 receptors A1R (PDB: 5N2S), which could cause heart failure and Alzheimer's disease. It was discovered that both compounds show promising results against the three targets. However, benzocoumarin shows an advantage over coumarin compounds. The effects of modifications to the coumarin core have been studied using an in silico technique that evaluates pharmacokinetics, absorption, distribution, metabolism, excretion, and toxicity of these compounds, showing promising results as an early-stage drug. However, both compounds were predicted to be highly absorbed from the gastrointestinal tract and enter the blood-brain barrier efficiently. The predicted oral toxicity of both compounds was LD50 = 350 mg/kg, putting both of them in the IV toxicity class. The optical properties of coumarin and benzocoumarin compounds were also investigated.