Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex against triple negative mammary carcinoma.

A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non­platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo. OVMI has been reported to generate cytotoxicity in human triple negative breast carcinoma cells, MDA-MB-231 as well as in mouse 4T1 cells by priming them for apoptosis. ROS-mediated, mitochondria-dependent as well as ER-stress-evoked apoptotic death seemed to be main operational hub guiding the cytotoxicity of OVMI in vitro. Moreover, OVMI has been noticed to elicit antimetastatic effect in vitro. Therapeutic application of OVMI has been extended on 4T1-based mammary tumor of female Balb/c mice, where it has been found to reduce tumor size, volume and restore general tissue architecture successfully to a great extent. Apart from that, OVMI has been documented to limit 4T1-based secondary pulmonary metastasis along with being non-toxic and biocompatible in vivo.

Multicolor x-rays from free electron-driven van der Waals heterostructures.

The emergence of van der Waals (vdW) heterostructures has led to precise and versatile methods of fabricating devices with atomic-scale accuracies. Hence, vdW heterostructures have shown much promise for technologies including photodetectors, photocatalysis, photovoltaic devices, ultrafast photonic devices, and field-effect transistors. These applications, however, remain confined to optical and suboptical regimes. Here, we theoretically show and experimentally demonstrate the use of vdW heterostructures as platforms for multicolor x-ray generation. By driving the vdW heterostructures with free electrons in a table-top setup, we generate x-ray photons whose output spectral profile can be user-customized via the heterostructure design and even controlled in real time. We show that the multicolor photon energies and their corresponding intensities can be tailored by varying the electron energy, the electron beam position, as well as the geometry and composition of the vdW heterostructure. Our results reveal the promise of vdW heterostructures in realizing highly versatile x-ray sources for emerging applications in advanced x-ray imaging and spectroscopy.

Oxidative stress imposed in vivo anticancer therapeutic efficacy of novel imidazole-based oxidovanadium (IV) complex in solid tumor.

Vanadium is a transitional metal having several therapeutic aspects that can be exploited for its anticancer activity. Herein, we have verified anticancer effectivity of synthesized novel water soluble mononuclear dipicolinic acid-1-allyl imidazole-based oxidovanadium (IV) complex [VOL(1-allylimz)2] with respect to anticancer effectivity of known standard platinum-based anticancer agent cisplatin. In current work, we have verified VOL(1-allylimz)2 as highly potential anticancer agent selectively against human breast cancer cells. VOL(1-allylimz)2 has been noticed to elicit dose dependent cytotoxicity in MCF-7 cell line through induction of intracellular oxidative stress and mitochondrial membrane potential. Apart from in vitro validation, in vivo studies in male Swiss Albino mice also have seen to portray dose-dependent anticancer effect of [VOL(1-allylimz)2], where indications of oxidative stress induction became prominent too. Besides, both mitochondrial as well as extra-mitochondrial apoptosis in tumor cells have been shown to be induced by [VOL(1-allylimz)2] treatment, together enforcing its anticancer potency. In contrast to cisplatin, which shows high chances of nephrotoxicity in cancer patients, [VOL(1-allylimz)2] has been found to be comparatively safe for in vivo studies.

Enhanced Versatility of Table-Top X-Rays from Van der Waals Structures.

Van der Waals (vdW) materials have attracted much interest for their myriad unique electronic, mechanical, and thermal properties. In particular, they are promising candidates for monochromatic, table-top X-ray sources. This work reveals that the versatility of the table-top vdW X-ray source goes beyond what has been demonstrated so far. By introducing a tilt angle between the vdW structure and the incident electron beam, it is theoretically and experimentally shown that the accessible photon energy range is more than doubled. This allows for greater versatility in real-time tuning of the vdW X-ray source. Furthermore, this work shows that the accessible photon energy range is maximized by simultaneously controlling both the electron energy and the vdW structure tilt. These results will pave the way for highly tunable, compact X-ray sources, with potential applications including hyperspectral X-ray fluoroscopy and X-ray quantum optics.

New mononuclear and binuclear oxomolybdenum(V) complexes containing NN chelator: Syntheses, DFT calculations, interaction with BSA protein and in vitro cytotoxic activity.

A neutral bidentate ligand 2-(3-methyl-5-phenyl pyrazol-1-yl) benzthiazole (L) has been synthesized by refluxing equimolar proportions of 2-hydrazino benzthiazole and benzoyl acetone in ethanol. The ligand acts in a NN donor fashion and forms stable mononuclear, MoOX3L [L = Ligand, X = Cl (1), Br (2)] and binuclear Mo2O4X2L2 [L = Ligand, X = Cl (3), Br (4)] complexes with molybdenum(V). The ligand and complexes are thoroughly characterized by elemental analyses, IR, UV-Vis spectroscopy, EPR study, magnetic susceptibility, thermogravimetry and cyclic voltammetry. Magnetic moment measurements reveal that the mononuclear complexes are paramagnetic while the binuclear complexes are diamagnetic in nature. EPR studies also confirm the presence of a mononuclear Mo(V) moiety in the complexes. Relevant Density Functional Theory (DFT) calculations have been carried out to determine the structures of the synthesized compounds. The binding mode and mechanism of interaction of the synthesized compounds with bovine serum albumin (BSA) were studied by concentration dependent absorption and fluorescence titration experiments. The ligand and complexes 1-4 are screened for their potential in vitro anticancer activities against three different human cancer cell lines, namely, cervix adenocarcinoma epithelial cells (HeLa), renal carcinoma cells (SK-RC-45) and breast adenocarcinoma cells (MCF-7). The oxomolybdenum(V) complexes are found to exhibit higher anticancer potency towards the cancer cells than the free ligand. Also, structure activity relationship (SAR) studies of this new series of oxomolybdenum(V) complexes indicate that the anticancer activity is to some extent dependent on the electronic effects of the halogen atom coordinated to the molybdenum centre.

Characterization and Inception of a Triterpenoid Astrakurkurol, as a Cytotoxic Molecule on Human Hepatocellular Carcinoma Cells, Hep3B.

Mushrooms are customary influential sources of pharmaceutically active metabolites. Usually lanostane-type triterpenoids from mushrooms had prospective for cancer disease treatments. Recently, a triterpenoid, astrakurkurol obtained from the fresh basidiocarps of the edible mushroom Astraeus hygrometricus, drew attention as a new cytotoxic therapeutic. The structural stability of this triterpenoid had been established with the amalgamation of density functional theory (DFT) calculations and study of single-crystal X-ray diffraction. To successfully manifest astrakurkurol as a potent cytotoxic therapeutics, a wide apprehension on the molecular and cellular mechanisms underlying their action is prerequisite. On this account, our study was directed to scrutinize the influence of this triterpenoid on human hepatocellular cancer cell model Hep3B. Encapsulating all experimental facts revealed that astrakurkurol had significantly decreased cell viability in a concentration-dependent manner. This effect was unveiled to be apoptosis, documented by DNA fragmentation, chromatin condensation, nuclear shrinkage, membrane blebing, and imbalance of cell cycle distribution. Astrakurkurol persuaded the expression of death receptor associated proteins (Fas), which triggered caspase-8 activation following tBid cleavage. Moreover, tBid mediated ROS generation, which triggered mitochondrial dysfunction and activated the mitochondrial apoptotic events. Astrakurkurol cytotoxicity was based on caspase-8-mediated intrinsic apoptotic pathway and was associated with inhibition at Akt and NF-κB pathway. Astrakurkurol had also inhibited the migration of Hep3B cells, indicating its antimigratory potential. These findings led us to introduce astrakurkurol as a feasible and natural source for a safer cytotoxic drug against hepatocellular carcinoma.

Syntheses, crystal structures, DFT calculations, protein interaction and anticancer activities of water soluble dipicolinic acid-imidazole based oxidovanadium(iv) complexes.

Three novel water soluble neutral mononuclear oxidovanadium(iv) complexes 1-3, [VOLB2] (where H2L = dipicolinic acid (DPA) and B = imidazole (1)/1-methylimidazole (2)/1-allylimidazole (3)), were synthesized by the reaction of [VOL(H2O)2] with imidazole/1-methylimidazole/1-allylimidazole in ethanol. The complexes were thoroughly characterized by elemental analysis, IR, UV-Vis and EPR spectroscopy, magnetic susceptibility, cyclic voltammetry and single crystal X-ray diffraction techniques. In all the complexes the vanadium(iv) centre assumes a distorted octahedral environment. All the three complexes have similar structures and contain a range of intramolecular interactions such as hydrogen bonding, C-Hπ, and ππ stacking dominating their supramolecular architectures. A thermal study of the complexes was carried out to analyze their stability. The energy of non-covalent interactions and frontier orbitals for the complexes were also calculated by DFT. In order to investigate the binding interactions and conformational changes of the secondary structure of bovine serum albumin (BSA) with the complexes, absorption, fluorimetric titration and circular dichroism measurements in aqueous medium were carried out. Molecular docking studies have also been carried out to understand the binding modes and interaction patterns of the oxidovanadium(iv) complexes with BSA. The anticancer activities of the ligand and complexes 1-3 were tested against the human hepatic carcinoma cell line Hep3B. The complexes showed prominent cytotoxicity towards cancer cells.

Exploring the mechanism of electron transfer between DNA and a ternary copper complex.

Photoinduced intramolecular electron transfer occurs in the triplet state within the complex [Htyr-Cu-phen](+) (Htyr = l-tyrosinato; phen = 1,10-phenanthroline) from tyrosine to phenanthroline. For this linked donor-acceptor system, a prominent magnetic field effect (MFE) is observed for the triplet-born radicals. The competitive binding study in the presence of ethidium bromide suggests that the complex interacts with calf thymus DNA (CT DNA) through partial intercalation. The photoexcited copper complex can oxidize DNA in a deoxygenated environment. Though the oxidation of tyrosine is thermodynamically more favorable than the oxidation of guanine, the primary electron transfer occurs from the DNA base to the phen ligand. A prominent MFE is observed for this noncovalently bound triplet-born guanine radical and phen radical anion. The process of partial intercalation of the copper complex within DNA is responsible for this rare observation.

Magnetic field effect on photoinduced electron transfer between [Cu(phen)2]2+ and DNA.

The magnetic field effect (MFE) on the photoinduced electron transfer (PET) reaction between the [Cu(phen)2]2+ complex and DNA has been studied in homogeneous buffer medium and in reverse micelles. The copper complex on photoexcitation can oxidize DNA in a deoxygenated environment. A prominent MFE is found even in a homogeneous aqueous medium for the triplet born radicals. The process of partial intercalation of [Cu(phen)2]2+ complex within DNA is responsible for such a rare observation. In reverse micelles, the MFE is not very much prominent because of the large separation distance between the component radicals of the geminate radical ion pairs generated through PET.