Anticancer Behavior of Pyrrolidine-Based Palladium(II) Complexes and Biophysical Approach on Their DNA, BSA Binding Activity, Molecular Docking, and DFT Study.

A series of pyrrolidine-based Pd(II) complexes, [Pd(AEP)Cl2] (C-1), [Pd(AEP)(OH2)2]2+(C-2), [Pd(AEP)(L-cys)]+ (C-3), [Pd(AEP)(N-ac-L-cys)] (C-4), [Pd(AEP)(GSH)] (C-5), and [Pd(AEP)(DL-meth)]2+ (C-6) (where, AEP = 1-(2-aminoethyl)pyrrolidine, L-cys = l-cysteine, N-ac-L-cys = N-acetyl-l-cysteine, GSH = glutathione, and DL-meth = dl-methionine), as anticancer drug candidates have been synthesized and characterized. The DNA binding property of the complexes was executed by gel electrophoresis and spectrophotometric and viscometric methods, and their interaction with BSA was also investigated by various spectroscopic methodologies. The binding activity of the Pd(II) complexes with DNA and BSA were assessed to evaluate their binding mode and binding constants. Molecular docking was performed to correlate with the experimental results on the interaction of the complexes with DNA and BSA. The changes in the microenvironmental and structural properties of BSA are monitored by a synchronous and 3D fluorescence study. The structural properties were evaluated by DFT and TD-DFT studies. The anticarcinogenic activity of the Pd(II) complexes was assessed by PASS prediction software to corroborate with the experimental results of the anticancer activity of the complexes. The ROS generation in cancer cell lines has been investigated, and the cell death mechanism through apoptosis was confirmed by measuring the protein expression. All these complexes have excellent anticancer activity compared to ancillary ligands. The cancer cell line (HCT116) shows almost similar or better cell inhibition activity when treated with the Pd(II) complexes compared to cisplatin, whereas the adverse effect is minimum on a normal cell (NKE). Both the Pd(II) and Pt(II) complexes carrying the same ligands reveal almost similar antiproliferative activity.

Explicating the recognition phenomenon of hazardous nitro-aromatic compound from contaminated environmental and cellular matrices by rationally designed pyridine-functionalized molecular probes.

In the quest of recognizing hazardous nitro-aromatic compounds in water, two pyridine-functionalized Schiff-base chemosensors, DMP ((E)-N-(3,4-dimethoxybenzylidene)(pyridin-2-yl)methanamine)) and MP (4-((E)-((pyridin-2-yl)methylimino)methyl)-2-ethoxyphenol) have been synthesized to detect mutagenic 2,4,6-Trinitrophenol (TNP) in soil, water as well as cellular matrices by producing turn-off emission responses as a combined consequence of PET and RET processes. Several experimental analyses including ESI-MS, FT-IR, photoluminescence, 1H NMR titration, and the theoretical calculations ascertained the formation and sensing efficacies of the chemosensors. The analytical substantiations revealed that structural variation of the chemosensors played a significant role in improving the sensing efficiency, which would certainly be worthwhile in developing small molecular TNP sensors. The present work depicted that the electron density within the MP framework was more than that of DMP due to the intentional incorporation of -OEt and -OH groups. As a result, MP represented a strong interaction mode towards the electron-deficient TNP with a detection limit of 39 µM.

Brief Research on the Biophysical Study and Anticancer Behavior of Pt(II) Complexes: Their DNA/BSA Binding, Molecular Docking, and Cytotoxic Property.

The potent bidentate carrier ligand 2-picolylamine (pic) has been used to synthesize Pt(II) complexes to know their bioactivity and anticancer property as reflected by PASS prediction software. The dichloro Pt(II) complex [Pt(pic)Cl2], Pt-1, and its hydrolyzed diaqua complex [Pt(pic)(OH2)2]2+, Pt-2, were synthesized. The thiol-containing Pt(II) complexes [Pt(pic)(l-cys)]+, Pt-3, and [Pt(pic)(L-ac-l-cy)]+, Pt-4, were synthesized from Pt-2, which was obtained from hydrolysis of Pt-1. Their biomolecular interactions with BSA and DNA were executed by spectroscopic methods, and their cytototoxic property was tested by the MTT assay. In vitro biomolecular interactions of Pt(II) complexes with BSA and DNA were investigated by different spectroscopic and viscosity measurement methods for their pharmacokinetic and pharmacodynamic importance. The conformational change of BSA in the presence of a drug candidate was studied by Förster resonance energy transfer calculation and synchronous and three-dimensional fluorescence spectroscopic studies. A theoretical approach on optimization structures, highest occupied molecular orbital-lowest unoccupied molecular orbital energy, global reactivity parameters, time-dependent density functional theory, and molecular docking with BSA and DNA was executed to strengthen and support the experimental observations. In vitro cytotoxic profiles of the complexes like the anticancer activity and their level of reactive oxygen species production were brought under consideration on A549 cancer cells and the normal human embryonic kidney cell line HEK-293. The cytotoxic property was compared with that of the recognized anticancer drug cisplatin.

Cytotoxic effects of Pd(II) complexes on cancer and normal cells: Their DNA & BSA adduct formation and theoretical approaches.

Herein, we report the synthesis and characterisation of a series of Pd(II) complexes: Pd(TEEDA)Cl2, C-1; [Pd(TEEDA)(OH2)2](NO3)2, C-2; [Pd(TEEDA)(l-cys)](NO3)2, C-3; [Pd(TEEDA)(NALC)], C-4; [Pd(TEEDA)(Meth)](NO3)2, C-5; and [Pd(TEEDA)(GSH)], C-6 (where TEEDA = N,N,N'-Triethylenediamine, l-cys = l-cysteine, NALC = N-acetyl-l-cysteine, Meth = dl-methionine and GSH = glutathione). UV-Vis spectroscopic characterisation was supported by TD-DFT theoretical simulation using Gaussian09 software. Different reactivity parameters were calculated from the energy difference between HOMO and LUMO of the complexes by DFT. The bonding mode of the labile ligands was confirmed by NBO analysis. Interaction of the complexes with DNA has been observed by gel electrophoresis experiment. DNA binding nature as well as binding constants of the complexes were measured with UV-Vis and fluorescence spectroscopic method. The binding nature of the complexes with DNA was confirmed by viscometric titration. Interaction of the complexes with BSA was investigated by UV-Vis and fluorescence titration method. Cytotoxic activity of the Pd(II) complexes was evaluated on A549 (lung carcinoma epithelial cells), HCT116(Colorectal Carcinoma) and HEK293 (Human embryonic kidney cells) cell lines. The ROS generation in the presence of the complexes was tested both on cancer cell lines A549 and HCT116 as well as human normal cell HEK293.

Theoretical investigation on hydrolysis mechanism of cis-platin analogous Pt(II)/Pd(II) complex by DFT calculation and molecular docking approach for their interaction with DNA & HSA.

The properties to be an active drug candidate of the complex Pt(TEEDA)Cl2, C1; Pd(TEEDA)Cl2, C2 and their hydrolysed product [Pt(TEEDA)(OH2)2]2+, C1' and [Pd(TEEDA)(OH2)2]2+, C2' were predicted by Lipinski's rule of 5 and PASS (prediction of activity spectra for substances) web tool. Their structural profile, HOMO-LUMO energy and electronic potential surface ware analysed by DFT calculation. Their TD-DFT spectra were compared with experimental UV-Vis spectra. The hydrolysis mechanisms of C1 & C2 to the diaqua form C1' and C2' were extensively investigated by DFT method in different levels of theory and using CPCM/water model and compared with recognised Pt based anticancer drugs. All the stationary states, including the transition state for the reactions were identified by the DFT calculation. The IRC calculation confirmed that the transition states are well connected and corelate with reactants and products. Interaction of the complexes with DNA & HSA was also investigated by molecular docking study.