European Journal of Biomedical and Pharmaceutical Sciences

NITROGEN BRIDGED IMIDAZO PYRIMIDINE ACETAMIDES: SYNTHESIS, MOLECULAR DOCKING, TOXICITY PREDICTION AND ANTI-PROLIFERATIVE STUDIES

Sruthi K.*, Sumakanth M., Mahendra Kumar C.B. and Naresh K.

ABSTRACT

In the present investigation new series of imidazo[1,2-a]pyrimidines were designed and synthesized by the reaction of various 4-Substituted aryl 2-methyl oxazole 5-ones(2a-2n) with the 2-amino pyrimidine. The formation of imidazo[1,2-a] pyrimidine acetamides(4a-n) were further confirmed by the physical, IR, NMR and mass spectra and elemental analysis. All the compounds (4a-4n) were screened for anti proliferative activity by employing MTT assay on A549 lung cancer cell lines. From the in vitro antiproliferative screening results it was concluded that compounds 4n(IC50 value 1.4 μmol), 4c(IC50 value 2.1 μmol), and 4i (IC50 value 2.6 μmol), are potent antiproliferative agents,whereas, the other compounds tested were less potent than the standard drug (Dabrafenib IC50 value 0.003 μmol). Molecular docking studies of these compounds were carried out to assess the ability of these compounds to bind and inhibit the B-Raf kinase using Autodock and Schrodinger. In the docking studies it was observed that compounds 4n, 4c, 4h and 4i are good ligands for inhibition of the B-raf kinase. All the designed compounds were subjected to molecular property prediction by using OSIRIS property explorer for liphophilicity, solubility and drug likeness. The toxicity profile of the molecules was also predicted to identify potentially toxic compounds, druglikeness and pharmacokinetic parameter such as percentage absorption in the series before being tested in other biological models.

Keywords: Imidazopyrimidinyl acetamide derivatives, 4-arylidene oxazolones, anti-proliferative activity. Osiris molecular property explorer.