The approaches to the synthesis of dialkylphosphorylpyridines and quinolones with cyclic and acylic phosphoryl-group was developed. A wide row of their Сu(II), Zn(II), Mn(II) and Ni(II) chelate complexes was synthesized. All obtained ligands and complexes were tested on the cytotoxic activity towards M-Hela and HuTu80 cancer cells as well towards Chang Liver normal cell line. N-heterocycle-containing phosphine oxides themselves are low toxic against Chang Liver normal as well as M-Hela and HuTu80 cancer cell lines, whereas the chelation with a metal ion selectively enhances the cytotoxicity of ligands against cancer cells. Mn(II), Cu(II), and Zn(II) complexes of diisopropylphosphorylquinoline and 1,3,5-diazaphosphorinane P-pyridyl-P-oxide exhibit the high cytotoxicity towards cancer cells with high selectivity (the selectivity index achieves  the values of 15 and 17) exceeding selectivity of known anticancer drugs tamoxifen, doxorubicin, oligomycin, 5-fluorouracil and sorafenib The approaches to the synthesis of dialkylphosphorylpyridines and quinolones with cyclic and acylic phosphoryl-group was developed. A wide row of their Сu(II), Zn(II), Mn(II) and Ni(II) chelate complexes was synthesized. All obtained ligands and complexes were tested on the cytotoxic activity towards M-Hela and HuTu80 cancer cells as well towards Chang Liver normal cell line. N-heterocycle-containing phosphine oxides themselves are low toxic against Chang Liver normal as well as M-Hela and HuTu80 cancer cell lines, whereas the chelation with a metal ion selectively enhances the cytotoxicity of ligands against cancer cells. Mn(II), Cu(II), and Zn(II) complexes of diisopropylphosphorylquinoline and 1,3,5-diazaphosphorinane P-pyridyl-P-oxide exhibit the high cytotoxicity towards cancer cells with high selectivity (the selectivity index achieves  the values of 15 and 17) exceeding selectivity of known anticancer drugs tamoxifen, doxorubicin, oligomycin, 5-fluorouracil and sorafenib