👤 Singh RK

The six mononuclear Schiff's base Ru(III) complexes viz., [Ru(BZP)(LA)₂].2NO₃ (MRA), [Ru(BZP)(LB)₂].2NO₃ (MRB), [Ru(BZP))(LC)₂].2NO₃ (MRC), [Ru(BZP))(LD)₂].2NO₃ (MRD), [Ru(BZP)(LE)₂].2NO₃ (MRE) and [Ru(BZP)(LF)₂].2NO₃ (MRF), were synthesized using of (BZP=2,6-bis(2-benzimidazolyl)pyridine and p-sub-benzylthiosemicarbazones (BTS) [(Sub=4-NO₂ (LA), 4-N(CH₃)₂ (LB), 4-Cl (LC), 4-OCH₃ (LD), 4-OCH₂Ph (LE), and 4-OH (LF)] as an ancillary ligands. The thiosemicarbazones ligands (LA-LF) were obtained by the condensation of p-substituted benzaldehyde and thiosemicarbazide. These complexes were characterized by elemental analysis, IR, ESR, ESI-MS, electronic absorption spectroscopy. The geometry was optimized by theoretical calculation using DFT and structure reveals that MRA-MRF adopt octahedral geometry. Further, the complexes were examined for anti-cancer against Leukemia cancer cell line K562 and shown significant responses to these cells. Moreover, DNA binding studies were conducted with all complexes MRA-MRF and the binding constant (K_b) were found i.e., 1.10×10⁴, 1.54×10⁴, 2.87×10⁴, 1.67×10⁴, 1.98×10⁴ and 1.59×10⁴, respectively. It was found that DNA binds in intercalation mode which is also validated by the docking studies. Show less

A series of nine new complexes of ruthenium(II), rhodium(III), and iridium(III) incorporated with pyrazoline-based ligands were synthesized and characterized by various spectroscopic techniques such as FTIR, ¹H NMR, ¹³C NMR, UV-Vis spectroscopy, ESI-MS spectrometry and X-ray crystallographic studies. All the synthesized compounds were assessed for their antibacterial abilities against Gram-positive and Gram-negative bacterial strains. The compounds showed better antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus Thuringiensis), with activities superior to standard kanamycin. Antioxidant studies revealed the mild radical scavenging proficiency of the compounds. DNA binding studies using fluorescence spectroscopy showed that the compounds could bind to Salmon Milt DNA electrostatically via external contact and groove surface binding with moderate affinity. The synthesized complexes were tested for anticancer activity using cell cytotoxicity and apoptosis assays in Dalton's lymphoma (DL) cell lines. The findings were compared to cisplatin (the standard drug) under identical experimental conditions. The cell viability results showed that complex 7 induced higher cytotoxicity in the DL cell line than the other tested compounds. The results of the molecular docking analysis further suggest that selective complexes have complete contact with the active amino acids sites of anti-apoptotic Bcl-2 family protein. Show less

In this paper a novel ligand debip (2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f] [1, 10]phenanthroline) and its Ru(II) polypyridyl complexes [Ru(L)₂(debip)]²⁺, (L = phen (1), bpy (2) and dmb (3)) have been synthesized and characterized by spectroscopic techniques. The DNA binding studies for all these complexes were examined by absorption, emission, quenching studies, viscosity measurements and cyclic voltammetry. The light switching properties of complexes 1-3 have been evaluated. Molecular docking, Density Functional Theory (DFT) and time dependent DFT calculations were performed. The Ru(II) complexes exhibited efficient photocleavage activity against pBR322 DNA upon irradiation and exhibited good antimicrobial activity. Also investigated 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, lactate dehydrogenase (LDH) release assay and reactive oxygen species (ROS) against selected cancer cell lines (HeLa, PC3, Lancap, MCF-7 and MD-MBA 231). Show less

The four novel Ru(II) polypyridyl complexes of [Ru(Hdpa)2dmbip](2+) (1), [Ru(Hdpa)2NO2-dmbip](2+) (2), [Ru(Hdpa)2debip](2+) (3) and [Ru(Hdpa)2OH-debip](2+) (4) where Hdpa = 2,2'-bipyridylamine, dmbip = 2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, debip = 2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, NO2-dmbip = NO2-2-(4-N,N-dimethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline, OH-debip = OH-2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f][1,10]phenanthroline were synthesized and fully characterized using elemental analysis, Mass, NMR and FT-IR. The DNA binding behavior of all synthesized complexes were investigated by using electronic absorption spectra, emission spectra, cyclic light switch on and off, sensor studies, electrochemical method and viscosity titrations. Docking studies were performed with human DNA TOP1 by using LibDock. Furthermore explore antimicrobial activity, photocleavage and in vitro cytotoxicity assay of four Ru(II) complexes. Show less

Four organometallic complexes [(η(6)-C6H6)RuCl(pmpzdpm)], 1; [(η(6)-C6H6)RuCl(pypzdpm)], 2; [(η(6)-C10H14)RuCl(pmpzdpm)], 3 and [(η(6)-C10H14)RuCl(pypzdpm)], 4 containing 5-(2-pyrimidyl-piperazine)phenyldipyrromethene (pmpzdpm) and 5-(2-pyridylpiperazine)phenyldipyrromethene (pypzdpm) have been designed and synthesized. The complexes 1-4 have been fully characterized by elemental analyses and spectroscopic studies (ESI-MS, IR, (1)H, (13)C NMR, UV-vis). Their electrostatic/intercalative interaction with CT DNA has been investigated by UV-vis and competitive ethidium bromide displacement studies while their protein binding affinity toward bovine serum albumin (BSA) was realized by UV-vis, fluorescence, synchronous and three dimensional (3D) fluorescence studies. The interaction with DNA and protein has further been validated by in silico studies. Cellular uptake, in vitro cytotoxicity and flow cytometric analyses have been performed to determine the mode of cell death against the kidney cancer cell line ACHN. Cell cycle analysis suggested that the complexes cause cell cycle arrest in the subG1 phase and overall results indicated that the in vitro antitumor activity of 1-4 lies in the order of 3 >4 >1 >2 (IC50, 7.0 1; 8.0 2; 2.0 3; 4.0 μM,4 ). Show less

Reactive oxygen species (ROS) are well known to be involved in oncogene-mediated cellular transformation. However, the regulatory mechanisms underlying ROS generation in oncogene-transformed cells are unclear. In the present study, we found that oncogenic K-Ras induces ROS generation through activation of NADPH oxidase 1 (NOX1), which is a critical regulator for the K-Ras-induced cellular transformation. NOX1 was activated by K-Ras-dependent translocation of p47(phox), a subunit of NOX1 to plasma membrane. Of note, PKCδ, when it was activated by PDPK1, directly bound to the SH3-N domain of p47(phox) and catalyzed the phosphorylation on Ser348 and Ser473 residues of p47(phox) C-terminal in a K-Ras-dependent manner, finally leading to its membrane translocation. Notably, oncogenic K-Ras activated all MAPKs (JNK, ERK and p38); however, only p38 was involved in p47(phox)-NOX1-dependent ROS generation and consequent transformation. Importantly, K-Ras-induced activation of p38 led to an activation of PDPK1, which then signals through PKCδ, p47(phox) and NOX1. In agreement with the mechanism, inhibition of p38, PDPK1, PKCδ, p47(phox) or NOX1 effectively blocked K-Ras-induced ROS generation, anchorage-independent colony formation and tumor formation. Taken together, our findings demonstrated that oncogenic K-Ras activates the signaling cascade p38/PDPK1/PKCδ/p47(phox)/NOX1 for ROS generation and consequent malignant cellular transformation. Show less