Synthesis, structure elucidation and biological evaluation of triple bridged dinuclear copper(II) complexes as anticancer and antioxidant/anti-inflammatory agents

Abstract

Seeking for copper based metallo-therapeutics, three triple bridged dinuclear copper(II) complexes [Cu₂(μ₂-L₂)(bipy)₂(μ₂-OH)(μ₂-H₂O)](NO₃)₂·H₂O (1·H₂O), [Cu₂(μ₂-L₂)(bipy)₂(μ₂-OH)(μ₂-NO₃)](NO₃)·0.6MeOH·0.4H₂O (2·0.6MeOH·0.4H₂O) and [Cu₂(μ₂-L₁)(bipy)₂(μ₂-OH)(μ₂-NO₃)(H₂O)](NO₃)·2H₂O (3·2H₂O) where L₂=2-thiophene acetato, L₁=2-thiophene carboxylato and bipy=2,2'-bipyridine were synthesized and structurally characterized. The complexes were subjected in vitro to a pharmacochemical evaluation for their antioxidant/anti-inflammatory activity, cytotoxicity and efficacy against human ovarian, lung, colon, breast, kidney and cervical cancer cell lines along with non tumor human lung and breast cell lines. The biological results support the structure related cytotoxic activity of the compounds. Complex 3 presented a combination of best anticancer and anti-inflammatory activities. A computational analysis over the LOX-3 protein structure 1JNQ was performed to support the possible mode of action.