Metal and Metal Oxides Nanoparticles and Nanosystems in Anticancer and Antiviral Theragnostic Agents.

The development of antiviral treatment and anticancer theragnostic agents in recent decades has been associated with nanotechnologies, and primarily with inorganic nanoparticles (INPs) of metal and metal oxides. The large specific surface area and its high activity make it easy to functionalize INPs with various coatings (to increase their stability and reduce toxicity), specific agents (allowing retention of INPs in the affected organ or tissue), and drug molecules (for antitumor and antiviral therapy). The ability of magnetic nanoparticles (MNPs) of iron oxides and ferrites to enhance proton relaxation in specific tissues and serve as magnetic resonance imaging contrast agents is one of the most promising applications of nanomedicine. Activation of MNPs during hyperthermia by an external alternating magnetic field is a promising method for targeted cancer therapy. As therapeutic tools, INPs are promising carriers for targeted delivery of pharmaceuticals (either anticancer or antiviral) via magnetic drug targeting (in case of MNPs), passive or active (by attaching high affinity ligands) targeting. The plasmonic properties of Au nanoparticles (NPs) and their application for plasmonic photothermal and photodynamic therapies have been extensively explored recently in tumor treatment. The Ag NPs alone and in combination with antiviral medicines reveal new possibilities in antiviral therapy. The prospects and possibilities of INPs in relation to magnetic hyperthermia, plasmonic photothermal and photodynamic therapies, magnetic resonance imaging, targeted delivery in the framework of antitumor theragnostic and antiviral therapy are presented in this review.

Copper coordination compounds with (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones. Comparison with sulfur analogue.

A series of new organic ligands (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones (L) consisting of two 5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-one units linked with polymethylene chains of various lengths (n = 2-10, where n is the number of CH2 units) have been synthesized. The reactions of these ligands with CuCl2·2H2O and CuClO4·6H2O gave Cu2+ or Cu1+ containing mono- and binuclear complexes with Cu2LCl x (x = 2-4) or CuL(ClO4) y (y = 1, 2) composition. It was shown that the agents reducing Cu2+ to Cu1+ in the course of complex formation can be both a ligand and an organic solvent in which the reaction is carried out. This fundamentally distinguishes the selenium-containing ligands L from their previously described sulfur analogs, which by themselves are not capable of reducing Cu2+ during complexation under the same conditions. A higher cytotoxicity and reasonable selectivity to cancer cell lines for synthesized complexes of selenium-containing ligands was shown; unlike sulfur analogs, ligands L themselves demonstrate a high cytotoxicity, comparable in some cases to the toxicity of copper-containing complexes.

Novel Copper-Containing Cytotoxic Agents Based on 2-Thioxoimidazolones.

A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure-activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40-60 µm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.

Influence of succinylation of a wide-pore albumin cryogels on their properties, structure, biodegradability, and release dynamics of dioxidine loaded in such spongy carriers.

The goal of this study was to reveal how the chemical modification, succinylation in this case, of the wide-pore serum-albumin-based cryogels affects on their osmotic characteristics (swelling extent), biodegradability and ability to be loaded with the bactericide substance - dioxidine, as well as on its release. The cryogels were prepared via the cryogenic processing (freezing - frozen storage - thawing) of aqueous solutions containing bovine serum albumin (50 g/L), denaturant (urea or guanidine hydrochloride, 1.0 mol/L) and reductant (cysteine, 0.01 mol/L). Freezing/frozen storage temperatures were either -15, or -20, or -25 °C. After defrosting, spongy cryogels were obtained that possessed the system of interconnected gross pores, whose shape and dimensions were dependent on the freezing temperature and on the type of denaturant introduced in the feed solution. Subsequent succinylation of the resultant cryogels caused the growth of the swelling degree of the pore walls of these spongy materials, resulted in strengthening of their resistance against of trypsinolysis and gave rise to an increase in their loading capacity with respect to dioxidine. With that, the microbiological tests showed a higher bactericidal activity of the dioxidine-loaded sponges based on the succinylated albumin cryogels as compared to that of the drug-carriers based on the non-modified protein sponges.

3-(2-Azidoethyl)oxindoles: Advanced Building Blocks for One-Pot Assembly of Spiro[pyrrolidine-3,3'-oxindoles].

A new synthetic approach to biologically relevant spiro[pyrrolidine-3,3'-oxindoles] was developed on the basis of the cascade transformation of 3-(2-azidoethyl)oxindoles via Staudinger/aza-Wittig/Mannich reactions. The parent azides were readily synthesized through a nucleophilic ring opening of spiro[cyclopropane-1,3'-oxindoles] with the azide ion. A series of new spiro[pyrrolidine-3,3'-oxindoles] with various (het)aryl substituents at the C2 and C5 positions of the pyrrolidine ring were synthesized. In vitro experiments revealed their high cytotoxicity toward LNCaP and PC-3 tumor cell lines.

Simple assembly of polysubstituted pyrazoles and isoxazoles via ring closure-ring opening domino reaction of 3-acyl-4,5-dihydrofurans with hydrazines and hydroxylamine.

A convenient general approach to 2-(pyrazol-4-yl)- and 2-(isoxazol-4-yl)ethanols based on the Brønsted acid-initiated reaction of 3-acyl-4,5-dihydrofurans with hydrazines or hydroxylamine was developed. Further transformation of the alcohol moiety in 2-(pyrazolyl)ethanols affording 2-(pyrazolyl)ethylamine as potent bioactive compounds as well as pyrazole-substituted derivatives of antitumor alkaloid crispine A was elaborated.

A bioinspired route to indanes and cyclopentannulated hetarenes via (3+2)-cyclodimerization of donor-acceptor cyclopropanes.

A novel Lewis acid-catalyzed domino (3+2)-cyclodimerization of 2-arylcyclopropane-1,1-diesters and related stepwise cross-reaction of two different cyclopropanes were developed. These processes provide efficient and highly stereoselective access to polyoxygenated indanes and cyclopentannulated heteroarene derivatives, which display significant cytotoxicity against several lines of cancer cells (IC50 of 10(-6)-10(-5) M) while being non-toxic for normal cells.

Duality of donor-acceptor cyclopropane reactivity as a three-carbon component in five-membered ring construction: [3+2] annulation versus [3+2] cycloaddition.

Quo vadis? The Lewis acid catalyzed reaction of (hetero)aryl-derived donor-acceptor cyclopropanes with alkenes can be selectively directed along a [3+2] annulation pathway (see scheme). This new process provides convenient and efficient access to indanes and other cyclopentannulated (hetero)arenes, among which polyoxygenated 1-arylindanes exhibit significant cytotoxicity against several cancer cell lines with an IC50 of 10(-6)-10(-5) M.