Deciphering the Mechanism of MRSA Targeting Copper(II) Complexes of NN2 Pincer-Type Ligands.

WHO lists AMR as one of the top ten global public health issues. Therefore, constant effort is needed to develop more efficient antimicrobial drugs. As a result, earth-abundant transition-metal complexes have emerged as an excellent solution. In this regard, new aminoquinoline-based copper(II) pincer complexes 1-3 were designed, synthesized, and characterized by modern spectroscopic techniques. It is worth mentioning that, at the highest concentration (1024 µg/mL) of complexes (1-3), the hemolysis was found to be <15%, implying their less toxicity. Further, the complexes effectively interfered with the growth of Gram positive MRSA and the fungus Candida albicans. Among them, complex 2 was promising (MIC = 16 µg/mL) against MRSA, which was better than the known antibacterial drug kanamycin (64 µg/mL) under identical conditions. The Alamar blue cell viability test and the MBC/MFC identified by spot assay were in accordance with MIC values. Moreover, the insilico studies explained the most probable mechanism of action as inhibition of cell wall biosynthesis and dysfunction of antibiotic sensing proteins. Similarly, the antifungal action might be due to the cell surface adhesion protein dysfunction by the complexes. Furthermore, we are expecting to draw these compounds for clinical applications.

Are Zn(II) pincer complexes efficient apoptosis inducers? a deep insight into their activity against A549 lung cancer cells.

To expand the array of chemotherapeutic drugs, earth-abundant metal complexes are found to be the future direction. In this regard, new zinc(II) complexes 1-3 of 8-aminoquinoline-based pincer ligands were synthesized, characterized and tested for their anticancer activity. The IC50 values of these complexes were estimated by an MTT assay to be 16.35-17.95 µM and 33.35-40 µM against A549 lung and MCF-7 breast cancer cells respectively. Among them, 3 was slightly better than the other complexes and, thus, subjected to detailed studies. Moreover, the ligand corresponding to 3 was less active against both the cell lines than the complex. Further, 3 showed no toxicity against normal fibroblast cell line L929, which instantly elevated the drug characteristic of our complex. An AO-EB staining assay revealed that 3 can induce apoptosis in A549, and it was quantified by flow cytometry as 22.77%. Moreover, the depolarization of the mitochondrial membrane potential determined by JC-1 staining indicated excess ROS production sites in the mitochondria, which was confirmed by carboxy-H2DCFDA staining. Interestingly, the present complexes show better activity than that of the standard drug cisplatin against A549 cells. Overall, the studies provided promising results that can be extended for clinical applications.

Carbazole appended trans-dicationic pyridinium porphyrin finds supremacy in DNA binding/photocleavage over a non-carbazolyl analogue.

A carbazolyl appended trans-pyridyl porphyrin (1) was synthesized and its dicationic form 2 was obtained by methylation of the pyridyl group. Copper and zinc complexes of porphyrin 2 (Cu(II), 3; Zn(II), 4) were isolated and characterized by various modern spectroscopic techniques. The DNA binding properties of 2, 3, and 4 have been explored against calf thymus-DNA (CT-DNA). DNA binding was quantized using the intrinsic binding constant (Kb) that was calculated by UV-visible absorption spectroscopy, and the value Kb = 1.6 × 106 M-1 for compound 2 reveals a better interaction of 2 towards CT-DNA than those of 3 (3.1 × 105 M-1) and 4 (3.4 × 105 M-1), which follows the order 2 > 4 > 3. The fluorescence quenching efficiency and ethidium bromide quenching assay also indicated a good binding affinity of all the compounds towards CT-DNA. Furthermore, the spectroscopic data suggest that the possible mode of interaction is intercalation. The docking studies were in accordance with the experimental results. Notably, DNA cleavage studies reveal that 2 shows better damage than 3 and 4 which is in accordance with the binding affinity order 2 > 4 > 3. The observed quantum yield (2: 0.65, 3: 0.33, and 4: 0.97) and no change in DNA cleavage in the presence of NaN3 reveal the involvement of singlet oxygen. The singlet excited state lifetimes were in the range of 6.3-1.2 ns. Furthermore, these porphyrins can be investigated as interesting photosensitizers in photodynamic therapy and photochemotherapy.