Design, Synthesis and Evaluation of a Series of Zinc(II) Complexes of Anthracene-Affixed Multifunctional Organic Assembly as Potential Antibacterial and Antibiofilm Agents against Methicillin-Resistant .

A novel class of zinc(II)-based metal complexes, i.e., [Zn(acdp)(μ-Cl)]·2HO (), [Zn(acdp)(μ-NO)]·2HO (), and [Zn(acdp)(μ-OCCF)]·2HO () (Cl = chloride; NO = nitrate; CFCO = trifluoroacetate) of anthracene-affixed multifunctional organic assembly, Hacdp (Hacdp = ,'-bis[anthracene-2-ylmethyl]-,'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), have emerged as promising antibacterial and antibiofilm agents in the domain of medicinal chemistry. Accordingly, complexes - were synthesized by utilizing Hacdp in combination with ZnCl, Zn(NO)·6HO, and Zn(CFCO)·HO respectively, in the presence of NaOH at ambient temperature. The complexation between Hacdp and Zn was delineated by a combined approach of spectrophotometric and spectrofluorometric titration studies. The stoichiometry of acdp/Zn in all three complexes is observed to be 1:2, as confirmed by spectrophotometric/spectrofluorometric titration data. Elemental analysis (C, H, N, Zn), molar conductance, FTIR, UV-vis, and thermoanalytical (TGA/DTA) data were effectively used to characterize these complexes. Besides, the structures of - were established by density functional theory (DFT) calculation using B3LYP/6-311G, specifying a self-assembled compact geometry with average Zn···Zn separation of 3.4629 Å. All three zinc complexes exhibited significantly high antibacterial and antibiofilm activity against methicillin-resistant (MRSA BAA1717). However, complex showed a more recognizable activity than and , with minimum inhibitory concentration (MIC) values of 200, 350, and 450 μg/mL, respectively. The antimicrobial activity was tested by employing the minimum inhibitory concentration (MIC) and time-kill assay. The crystal violet (CV) assay and microscopic study were performed to examine the antibiofilm activity. As observed, complexes - had an effect on the production of extracellular polymeric substance (EPS), biofilm cell-viability, and other virulence factors such as staphyloxanthin and hemolysin production, autoaggregation ability, and microbial cell-surface hydrophobicity. Reactive oxygen species (ROS) generated due to inhibition of staphyloxanthin production in response to - were also analyzed. Moreover, complexes - showed an ability to damage the bacterial cell membrane due to accumulation of ROS resulting in DNA leakage. In addition, complexes - displayed a synergistic/additive activity with a commercially available antibiotic drug, vancomycin, with enhanced antibacterial activity. On the whole, our investigation disclosed that complex could be a promising drug lead and attract much attention to medicinal chemists compared to and from therapeutic aspects.