Spectroscopic and theoretical approach of DNA interaction and anticancer studies of bio-pharmaceutically active pyrimidine derived Cu(II) and Zn(II) complexes.

New metal(II) complexes (CuL2 and ZnL2) with pyrimidine appended Schiff base ligand (HL) were synthesized and characterized by diverse spectroscopic methods, reveals the proposed structure of metal(II) complexes possess square planar geometry. DNA interaction ability of isolated compounds was studied by UV-Visible, fluorescence, viscometric and electrochemical methods and the results showed that isolated compounds intercalated with calf thymus DNA (CT-DNA). In addition, anticancer activities of HL, CuL2, and ZnL2 have been evaluated by MTT assay, signifying moderate cytotoxic activity on selected cancer cell lines and less toxicity on NHDF normal cell line due to the specific targeting of pyrimidine analogues. Moreover, antioxidant activities of isolated compounds towards diverse free radicals have been studied by spectrophotometric methods. These results showed that CuL2 has better antioxidant ability than HL and ZnL2. Finally, antimicrobial activities of isolated compounds against selected antimicrobial pathogens exposed that CuL2 has better antimicrobial activity on E. coli and C. albicans than other antimicrobial pathogens. The DFT calculations have been done to get the optimized geometry of the ligand and the metal complexes. In order to get a broad understanding of the interactions of these synthesized metal complexes, a detailed molecular docking analysis is taken up.

Spectro-electrochemical, fluorometric and biothermodynamic evaluation of pharmacologically active morpholine scaffold single crystal ligand and its metal(II) complexes: A comparative study on in-vitro and in-silico screening towards DNA/BSA/SARS-CoV-19.

A novel series of metal(II) complexes (1-5) [MII(L)2]{Where M = Cu (1), Co (2), Mn (3), Ni (4) and Zn (5)} constructed from 2-(4-morpholinobenzylideneamino)phenol Schiff base ligand (HL) in a 1:2 M ratio and the spectral and analytical results put forward square planar geometry. Spectro-electrochemical, hydrodynamic, gel electrophoresis, and DNA binding/cleavage results for all the compounds demonstrate that complex (1) had excellent DNA binding/cleavage properties compared to other compounds. The observation also suggests that test compounds could intercalate with DNA, and the biothermodynamic property more strongly supports the stabilizing of the double helix DNA with the complexes. BSA binding constant results show that complex (1) exposes the best binding property via a static mode, which is further confirmed by FRET calculations. The DFT calculations and docking results for all compounds towards DNA, BSA and SARS-CoV-19 main protease (3CLPro), reveal the binding energies were in the range of -7.8 to -9.4, -6.6 to -10.2 and - 6.1 - -8.2 kcal/mol for all test compounds respectively. In this case, complexes showed favorable binding energies compared to free ligand, which stimulates further studies aimed at validating the predicted activity as well as contributing to tackling the current and future viral pandemics. The in-vitro antioxidant, antimicrobial, and anticancer results for all compounds revealed that copper complex (1) has better activity compared to others. This might result in an effective anticancer drug for future research, which is especially promising since the observed experimental results for all cases were in close agreement with the theoretical calculations.

Spectro-electrochemical assessments of DNA/BSA interactions, cytotoxicity, radical scavenging and pharmacological implications of biosensitive and biologically active morpholine-based metal(ii) complexes: a combined experimental and computational investigation.

Biosensitive and biologically active morpholine-based transition metal(ii) complexes (1-5) were constructed as [MII(L) AcO]·nH2O {where M = Cu (1) n = 1; Co (2), Mn (3), Ni (4), n = 4 and Zn (5) n = 2}, which were synthesized from 2-(-(2-morpholinoethylimino) methyl)-4-bromophenol ligand (HL) and structurally characterized by various analytical and spectroscopic techniques, which proposed a square planar and tetrahedral geometry around the central metal ion with lattice water molecules. The gel electrophoresis results revealed that complexes 1 and 5 had more potent DNA cleavage efficacy in the presence of an oxidizing agent (H2O2) as compared to the others. The observed DNA binding results for all the compounds as determined by spectro-electrochemical and hydrodynamic techniques were in the order 3.36 (1) > 3.06 (2) > 2.73 (4) > 2.61 (5) > 1.84 (3) > 1.00 (HL) × 104 M-1. The obtained bovine serum albumin (BSA) protein binding constant (K b) results put forward the following order 2.38 (1) > 2.21 (2) > 2.18 (5) > 1.76 (4) > 1.40 (3) > 1.26 (HL) × 104 M-1. Also, the biothermodynamic parameters (, , ΔH° and ΔS°) and binding results divulged that all the complexes (1-5) could bind to DNA via intercalation in a spontaneous manner. Density functional theory calculations were employed to optimize the structure of ligand (HL) and its complexes (1-5) to gain insights into their electronic structures. Molecular docking analysis was carried out to identify the preferential binding modes of these complexes toward DNA and BSA protein. The theoretical observations of all cases were found to be very close to the experimental observations. Among the radical scavenging activity results for all the cases toward DPPH, hydroxyl radical, superoxide, nitric oxide and ferric reducing agents, complex (1) revealed a superior scavenging potency over the other compounds. In the screened antimicrobial reports against 10 different selected pathogenic species, although all the complexes (1-5) exhibited a greater significant inhibitory effect than the free ligand, complexes 4 and 5 achieved the best potency over standard drugs. The observed percentage of growth inhibition for all the compounds against the A549, HepG2, MCF-7 and NHDF cell lines suggested that complex 1 had enhanced growth-inhibitory potency over the other compounds and slightly affected normal cells as compared to the standard drug cisplatin, which may lead to its investigation as a promising anticancer agent in future research.

Natural alkaloid Luotonin A and its affixed acceptor molecules: Serum albumin binding studies.

Effective interaction of natural alkaloid Luotonin A (L) and its affixed acceptor molecules 1 and 2 with donor molecule as Bovine serum albumin (BSA) at various pH (4.0, 7.4 and 10.0) medium have been demonstrated using various conventional spectroscopic techniques. These analyses provide some valuable features on the interaction between BSA and acceptor molecules (L, 1 and 2). From the absorption and fluorescence spectral titration studies, the formation of ground-state complexes between the acceptor molecules (L, 1 and 2) and the BSA have been confirmed. The results of the afore titrations analysis reveal that, the strong binding of receptor 1 with BSA (Kapp 5.68×104M-1; KSV 1.86×106Lmol-1; Ka 6.42×105Lmol-1; Kass 8.09×106M-1; ΔG -33.35kJ/mol) at physiological pH medium (7.4) than other receptor molecules 2 and L. The Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residues of BSA and acceptor molecules L, 1 and 2 during the interaction, are 28.85, 85.24 and 53.25 % respectively. The superior binding efficacy of acceptor 1 at physiological pH condition has been further confirmed by FT-IR and Raman spectral analysis methods. Moreover, theoretical docking studies of acceptors L, 1 and 2 towards HSA have been demonstrated to differentiate their binding behaviours. It reveals that, acceptor 1 has the strongest binding ability with HSA through two hydrogen bonding and the Atomic contact energy (ACE) value of -483.96kcal/mol.

Biologically Active Cu(II), Co(II), Ni(II) and Zn(II) Complexes of Pyrimidine Derivative Schiff Base: DNA Binding, Antioxidant, Antibacterial and In Vitro Anticancer Studies.

A new pyrimidine derivative Schiff base ligand (HL) [HL = 2-(4,6-dimethylpyrimidin-2-ylimino)methyl)-4-nitrophenol] and its metal(II) complexes [CuL2] (1), [CoL2] (2), [NiL2] (3) and [ZnL2] (4) have been synthesized and characterized by several spectral techniques. The square planar geometry of the complexes 1-4 confirmed by UV-Visible, ESR and EI-mass spectral techniques. DNA binding study of the complexes 1-4 with Calf Thymus (CT) DNA using absorption spectral titration at different pH (4.0, 7.0 & 10.0) have been scrutinized that the complexes 1-4 bound by groove binding mode with significant binding constant values (K b  = 5.61 × 105 M-1 (1), 2.60 × 105 M-1 (2), 2.48 × 105 M-1 (3) and 6.98 × 104 M-1 (4) at pH = 10.0. Binding nature of the complexes 1-4 with CT DNA has further confirmed by emission, viscometry and cyclic voltammetry which also recommended that complexes 1-4 bound with CT DNA. The complexes 1-4 possessed effective scavenging effect during the DPPH and SOD radical scavenging method. The antibacterial activity of the complexes 1-4 was vetted against several bacterial strains and the results shows that the ligand (HL) and complexes 1-4 are more active in Bascillus subtilis. The anticancer activity of the complexes 1-4 was evaluated against Human Breast Cancer Cells (MCF-7), Human Cervical Cancer Cells (HeLa), Human Laryngeal Epithelial Carcinoma (HEp2) and Normal Human Dermal Fibroblast (NHDF) by MTT assay, which revealed that complexes 1 & 2 have modest activity against the cancer cell lines than ligand (HL) and complexes 3 & 4.