Targeting SARS-CoV-2 proteins: In Silico Investigation with Polypyridyl-based Zn(II)-Curcumin Complexes.

Herein, we have selected eight Zn(II)-based complexes viz., [Zn(bpy)(acac)Cl] (1), [Zn(phen)(acac)Cl] (2), [Zn(dppz)(acac)Cl] (3), [Zn(dppn)(acac)Cl] (4), [Zn(bpy)(cur)Cl] (5), [Zn(phen)(cur)Cl] (6), [Zn(dppz)(cur)Cl] (7), [Zn(dppn)(cur)Cl] (8), where bpy=2,2'-bipyridine, phen=1,10-phenanthroline, dppz=benzo[i]dipyrido[3,2-a:2',3'-c]phenazine, dppn=naphtho[2,3-i]dipyrido[3,2-a:2',3'-c]phenazine, acac=acetylacetonate, cur=curcumin and performed in silico molecular docking studies with the viral proteins, i.e., spike protein (S), Angiotensin-converting enzyme II Receptor protein (ACE2), nucleocapsid protein (N), main protease protein (Mpro), and RNA-dependent RNA polymerase protein (RdRp) of SARS-CoV-2. The binding energy calculations, visualization of the docking orientation, and analysis of the interactions revealed that these complexes could be potential inhibitors of the viral proteins. Among complexes 1-8, complex 6 showed the strongest binding affinity with S and ACE2 proteins. 4 exerted better binding affinity in the case of the N protein, whereas 8 presented the highest binding affinities with Mpro and RdRp among all the complexes. Overall, the study indicated that Zn(II) complexes have the potential as alternative and viable therapeutic solutions for COVID-19.

Antibacterial Photodynamic Therapy by Zn(II)-Curcumin Complex: Synthesis, Characterization, DFT Calculation, Antibacterial Activity, and Molecular Docking.

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.