Red light-controlled polymerase chain reaction

A 23-mer DNA “caged” at its 3′-terminus with a 9-anthracenyl moiety was prepared. It can be uncaged in the presence of photosensitizer (In(pyropheophorbide-a)chloride)-containing DNAs (9–12 mers) and upon irradiation with red light. This mixture of DNAs was used to design red-light controlled polymerase chain reaction

Triggering RNA Interference by Photoreduction under Red Light Irradiation

RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more suitable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is desirable to increase its selectivity, e.g., by a prodrug approach to activate the siRNAs upon external triggering, e.g., by using light. Red light is especially well suited for in vivo applications due to its low toxicity and higher tissue penetration. Known molecular (not nanoparticle-based) red-light-activatable siRNA prodrugs rely on singlet oxygen (1O2)-mediated chemistry. 1O2 is highly cytotoxic. Additionally, one of the side products in the activation of the known siRNA prodrugs is anthraquinone, which is also toxic. We herein report on an improved redlight-activatable siRNA prodrug, which does not require 1O2 for its activation. In fact, the 5′ terminus of the antisense strand is protected with an electron-rich azobenzene promoiety. It is reduced and cleaved upon red light exposure in the presence of Sn(IV)(pyropheophorbide a)dichloride acting as a catalyst and ascorbate as a bulk reducing agent. We confirmed the prodrug activation upon red light irradiation both in cell-free settings and in human ovarian cancer A2780 cells

2,2′-Dihydroxybiphenyl-3,3′-di­carb­aldehyde dioxime

The mol­ecule of the title compound, C14H12N2O4, lies across a crystallographic inversion centre situated at the mid-point of the C—C intra-annular bond. The mol­ecule is not planar, the dihedral angle between the aromatic rings being 50.1 (1)°. The oxime group is in an E position with respect to the –OH group and forms an intra­molecular O—H⋯N hydrogen bond. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link mol­ecules into chains propagating along [001]. The crystal structure is further stabilized by inter­molecular stacking inter­actions between the rings [centroid-to-centroid distance = 3.93 (1) Å], resulting in layers parallel to the bc plane

Red light activated “caged” reagents for microRNA research

“Caged” reagents for miRNA research (siRNA targeting EGFR, involved in miRNA maturation, and mimics of miR-20a, playing a key role in tumor formation and metastasis) were prepared. It was demonstrated that these reagents can be activated by non-toxic to cells red light both in cells and in cell free settings

μ-Peroxido-bis­[acetonitrile­bis­(ethyl­enediamine)­cobalt(III)] tetrakis(per­chlorate)

The title compound, [Co2(O2)(CH3CN)2(C2H8N2)4](ClO4)4, consists of centrosymmetric binuclear cations and perchlorate anions. Two CoIII atoms, which have a slightly distorted octa­hedral coordination, are connected through a peroxido bridge; the O—O distance is 1.476 (3) Å. Both acetonitrile ligands are situated in a trans position with respect to the O—O bridge. In the crystal, the complex cations are connected by N—H⋯O hydrogen bonds between ethyl­endiamine NH groups and O atoms from the perchlorate anions and peroxide O atoms

Artemisinin modulating effect on human breast cancer cell lines with different sensitivity to cytostatics

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment

Diaquabis­[3-(hydroxy­imino)­butanoato]nickel(II)

In the neutral, mononuclear title complex, [Ni(C4H6NO3)2(H2O)2], the Ni atom lies on a crystallographic inversion centre within a distorted octa­hedral N2O4 environment. Two trans-disposed anions of 3-hydroxy­imino­butanoic acid occupy four equatorial sites, coordinated by the deprotonated carboxyl­ate and protonated oxime groups and forming six-membered chelate rings, while the two axial positions are occupied by the water O atoms. The O atom of the oxime group forms an intra­molecular hydrogen bond with the coordinated carboxyl­ate O atom. The complex mol­ecules are linked into chains along b by hydrogen bonds between the water O atom and the carboxyl­ate O of a neighbouring mol­ecule. The chains are linked by further hydrogen bonds into a layer structure

2-Hydroxy­amino-2-oxoacetohydrazide

In the title compound, C2H5N3O3, the hydroxamic group adopts an anti orientation with respect to the hydrazide group. In the crystal, mol­ecules are connected by N—H⋯O and O—H⋯N hydrogen bonds into zigzag chains along the c axis

Aminoferrocene‐Based Anticancer Prodrugs Labelled with Cyanine Dyes for in vivo Imaging

Abstract N‐alkylaminoferrocene‐based (NAAF) prodrugs are activated in the presence of reactive oxygen species (ROS), based on which these prodrugs target cancer cells (high ROS) and do not affect normal cells (low ROS). To gain some insights into their mode of action in vivo, we have investigated the biodistribution of 18F‐labelled NAAF prodrugs in tumor‐bearing mice by positron emission tomography (PET). Due to the short half‐life of 18F, the experimental time frame was restricted to 60 min. To extend the observation window, a more stable marker is required. In this paper, we report on conjugates of NAAF prodrugs with two cyanine dyes Cy5 and Cy7 including details of their synthesis, characterization and basic properties in cell free settings and their cellular uptake in representative human cancer cells. Finally, the Cy5 conjugate was subjected to in vivo fluorescence imaging studies to determine the prodrug biodistribution over 24 h

Diaquabis­[3-(hydroxy­imino­)butanoato]nickel(II): a triclinic polymorph

The title centrosymmetric mononuclear complex, [Ni(C4H6NO3)2(H2O)2], is a polymorph of the previously reported complex [Dudarenko et al. (2010 ▶). Acta Cryst. E66, m277–m278]. The NiII atom, lying on an inversion center, is six-coordinated by two carboxyl­ate O atoms and two oxime N atoms from two trans-disposed chelating 3-hydroxy­imino­butanoate ligands and two axial water mol­ecules in a distorted octa­hedral geometry. The hydr­oxy group forms an intra­molecular hydrogen bond with the coordinated carboxyl­ate O atom. The complex mol­ecules are linked in stacks along [010] by a hydrogen bond between the water O atom and the carboxyl­ate O atom of a neighboring mol­ecule. The stacks are further linked by O—H⋯O hydrogen bonds into a layer parallel to (001)