Novel α-Aminophosphonates of imatinib Intermediate: Synthesis, anticancer Activity, human Abl tyrosine kinase Inhibition, ADME and toxicity prediction.

An efficient method for the synthesis of a new class of α-aminophosphonates of imatinib derivative has been developed in one-pot Kabachnik-Fields reaction of N-(5-amino-2-methyl phenyl)-4-(3-pyridyl)-2-pyrimidine amine with various aldehydes and diethyl phosphite under microwave irradiation and neat conditions using NiO nanoparticles as an reusable and heterogeneous catalyst, with 96% yield at 450 W within 15 min. All the compounds were evaluated for their in vitro cytotoxicity with various cancer cell lines by MTT assay method. Compounds with halo (4f, -4Br, IC50 = 1.068 ± 0.88 µM to 2.033 ± 0.97 µM), nitro substitution (4 h, -3NO2, IC50 = 1.380 ± 0.94 µM to 2.213 ± 0.64 µM), (4 g, -4NO2, IC50 = 1.402 ± 0.79 µM to 2.335 ± 0.73 µM) and (4i, 4-Cl, 3-NO2, IC50 = 1.437 ± 0.92 µM to 2.558 ± 0.76 µM) were showed better anticancer activity when compared with standard drugs Doxorubicin and Imatinib using MTT assay method. Further in silico target hunting reveals the anticancer activity of the designed compounds by inhibiting human ABL tyrosine kinase and all the designed compounds have shown significant drug-like characteristics.

Meglumine as a green, efficient and reusable catalyst for synthesis and molecular docking studies of bis(indolyl)methanes as antioxidant agents.

An efficient and convenient Meglumine catalyzed procedure for the synthesis of bis(indolyl) methanes at ambient temperature under aqueous conditions in high yields. The catalytic reaction proceeds very smoothly. Clean reaction, ease of product isolation/purification, easily available reactants, metal free and environmentally friendly reaction conditions are the notable advantages of the present methodology. All the entitled compounds were characterized by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant (DPPH, H2O2 and NO scavenging methods). They exhibited potent in vitro antioxidant activity dose-dependently. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein. 4d exhibited marked binding affinity with excellent docking score of -7.6 K.cal/mol and emerged as a lead compound.

Facile synthesis, antioxidant and antimicrobial activity of amino methylene bisphosphonates.

A green and efficient preparation method for the amino bisphosphonates is accomplished by simple mixing and stirring of diethylphosphite, triethylorthoformate and various amines in the presence of amberlyst-15 as catalyst at room temperature under solvent free conditions. The title compounds are characterized by IR, (1)H-, (13)C-, (31)P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.