Studies on new dithiophosphonic acid derivatives: Synthesis, characterization, DFT and molecular docking calculations and in vitro cytotoxicity assessment

Abstract

Abstract 2,4-bis(3,4-dimethoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (SAV-A1) was treated with five different alcohols to obtain dithiophosphonic acids (HLn, HS2P((2,4-CH3O)2-C6H3)(ORn); n=1-5, R1=n-pentyl-; R2=2-pentyl-; R3=4-tert-but-benzyl-; R4=2-propyl-; R5=2-butyl-). HLn series were converted to their ammonium salts, ([NH4Ln]). [NH4Ln] were reacted with NiCl2.6H2O to obtain the corresponding Ni(II) coordination compounds ([Ni(Ln)2]) in ethanol medium. The structures of all the compounds were elucidated by spectroscopic techniques. Single-crystal X-ray diffraction analysis of [Ni(L1)2], [Ni(L2)2], [Ni(L4)2] and [Ni(L5)2] were also carried out. The ligands and their nickel complexes were tested on human liver and colon cancer cell lines using (MTT) assay method. The salts [NH4L2] and [NH4L5] demonstrated more antiproliferative effects than others in colon cancer cell line with IC50 values 82.73 and 74.87 µM, respectively. Density Functional Theory (DFT) calculations of [Ni(L1)2], [Ni(L2)2], [Ni(L4)2] and [Ni(L5)2] were done. The molecular docking studies of [Ni(L1)2], [Ni(L2)2], [Ni(L4)2] and [Ni(L5)2] with colon cancer antigen proteins, ID 2HQ6 and liver cancer protein, PDB ID: 3WZE were done to foresee the interactions of the complexes.