ABSTRACT
A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot three-component classical Kabachnik-Fields reaction in a green chemical approach by addition of an in situ generated dialkylphosphite to Schiff's base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2-alkylaminophosphonates were screened to in vitro antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. These in vitro studies have been further supported by ADMET (absorption, distribution, metabolism, excretion, and toxicity), quantitative structure-activity relationship, molecular docking, and bioactivity studies and identified that they were potentially bound to the GLN340 amino acid residue in chain C of 1DNU protein and TYR597 amino acid residue in chain A of 4M7E protein, causing potential exhibition of antioxidant and plant growth regulatory activities. Eventually, title compounds are identified as good blood-brain barrier (BBB)-penetrable compounds and are considered as proficient central nervous system active and neuroprotective antioxidant agents as the neuroprotective property is determined with BBB penetration thresholds.
ABSTRACT
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.
