Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents

New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag₂(barb)₂(μ-dppm)₂] (1), [Ag₂(barb)₂(μ-dppe)(DMSO)₂] (2) and [Ag₂(barb)₂(μ-dppp)₂] (3) were binuclear, while [Ag(barb)(μ-dppb)]_n (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies. All complexes displayed significant DNA cleavage in the presence of H₂O₂. 1-4 exhibited more specificity against Gram-positive bacteria than Gram-negative bacteria, but 2 targets both Bacterial strains, being comparable to AgNO₃ and silver sulfadiazine. Complex 1 has a strong growth inhibitory effect on A549 cells, while 2 and 3 exhibit considerable cytotoxicity against MCF-7 cells. The complexes showed high accumulation in the cytosol fraction of the cells. Mechanistic studies showed that 1 and 2 display effective cell growth inhibition by triggering S and G2/M phase arrest, induce Apoptosis via mitochondrial pathways and also damage to DNA due to the overproduction of ROS.

5,5-Diethylbarbiturate; Anticancer; Antimicrobial; Apoptosis mechanism; Bis(diphenylphosphino)alkane; Silver(I).