Silver(I) compounds of the anti-inflammatory agents salicylic acid and p-hydroxyl-benzoic acid which modulate cell function

Abstract

Silver nitrate reacts with salicylic acid (salH2) or p-hydroxy-benzoic acid (p-HbzaH2) and equimolar amount of NaOH to yield a white precipitations which are then treated with tri(p-tolyl)phosphine (tptp) or tri(m-tolyl)phosphine (tmtp) to yield the complexes [Ag(tptp)2(salH)] (1), [Ag(tptp)2(p-Hbza)] (2) and [Ag(tmtp)2(salH)] (3). Complexes 1 and 3 are also obtained when aspirin (aspH) is used. The acetic ester of salicylic acid is hydrolyzed to form the complexes 1 and 3. However, when aspirin and tptp are used, a mixture of products was obtained which contains both 1 and an ionic complex of formula {[Ag(tptp)4]+[(salH)−]∙[(CH3)2NCHO)]∙(H2O)} (1a). The complexes were characterized by m.p., e.a., mid-FT-IR, 1H-,31P-NMR, HRMS, UV–vis spectroscopic techniques and X-ray crystallography. Two phosphorus and one carboxylic oxygen atoms form a trigonal planar geometry around Ag(I) ions in complexes 1–3. Complex 1a consists of a [Ag(tptp)4]+ cation and a deprotonated salH− counter anion. The influence of 1–3 on the viability of MCF-7 (breast) and HeLa (cervix) adenocarcinoma cells, is evaluated. DNA binding tests indicate the ability of 1–3 to modify the activity of cells. The binding constants of 1–3 towards calf-thymus DNA, reveal stronger interaction of 2. Changes in fluorescent emission light of ethidium bromide (EB) in the presence of DNA suggest intercalation or electrostatic interactions into DNA for 1 and 3. Docking studies on DNA-complex interactions confirm the binding of 1–3 in the minor groove of B-DNA. Moreover, the influence of 1–3 on the peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.