Microwave assisted synthesis of 2-amino-4-chloro-pyrimidine derivatives: Anticancer and computational study on potential inhibitory action against COVID-19

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1–7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1–7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1–7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC(50) values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives (1–7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of −8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1–7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of −0.03 and −0.018, respectively and absence of AMES toxicity.