Enriching Chemical Space of Bioactive Scaffolds by New Ring Systems: Benzazocines and Their Metal Complexes as Potential Anticancer Drugs.

The search for new scaffolds of medicinal significance combined with molecular shape enhances their innovative potential and continues to attract the attention of researchers. Herein, we report the synthesis, spectroscopic characterization (H and C NMR, UV-vis, IR), ESI-mass spectrometry, and single-crystal X-ray diffraction analysis of a new ring system of medicinal significance, 5,6,7,9-tetrahydro-8-indolo[3,2-]benzazocin-8-one, and a series of derived potential ligands (), as well as ruthenium(II), osmium(II), and copper(II) complexes (, , and ). The stability of compounds in 1% DMSO aqueous solutions has been confirmed by H NMR and UV-vis spectroscopy measurements.

Different Modes of Acid-Promoted Cyclooligomerization of 4-(4-Thiosemicarbazido)butan-2-one Hydrazone: 14-Membered versus 28-Membered Polyazamacrocycle Formation.

Unprecedented self-assembly of a novel 14-membered cyclic bis-thiosemicarbazone or/and a 28-membered cyclic tetrakis-thiosemicarbazone upon acid-promoted cyclooligomerization of 4-(4-thiosemicarbazido)butan-2-one hydrazone has been discovered. A thorough study of the influence of various factors on the direction of macrocyclization provided the optimal conditions for the highly selective formation of each of the macrocycles in excellent yields. Plausible pathways for macrocyclizations have been discussed.

Synthesis and crystal structure of -di-aqua(1,4,8,11-tetra-aza-undeca-ne)copper(II) isophthalate monohydrate.

In the title hydrated mol-ecular salt, [Cu(CHN)(HO)](CHO)·HO, the metal ion is coordinated by the two primary and two secondary N atoms of the amine ligand and the mutually O atoms of the water mol-ecules in a tetra-gonally distorted octa-hedral geometry. The average equatorial Cu-N bond lengths (2.013 and 2.

Elucidation of Structure-Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action.

Indolo[3,2-][1]benzazepines (paullones), indolo[3,2-][2]benzazepines, and indolo[2,3-][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-][2]benzazepine-derived ligands - and copper(II) complexes -. All compounds were characterized by spectroscopic methods (H and C NMR, UV-vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes and , in addition, by X-ray crystallography.

Ready access to 7,8-dihydroindolo[2,3-][1]benzazepine-6(5)-one scaffold and analogues via early-stage Fischer ring-closure reaction.

Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-][1]benzazepin-6(5)-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring.

Highly Antiproliferative Latonduine and Indolo[2,3-]quinoline Derivatives: Complex Formation with Copper(II) Markedly Changes the Kinase Inhibitory Profile.

A series of latonduine and indoloquinoline derivatives - and their copper(II) complexes () were synthesized and comprehensively characterized. The structures of five compounds (, , , , and ) were elucidated by single crystal X-ray diffraction. The copper(II) complexes revealed low micro- to sub-micromolar IC values with promising selectivity toward human colon adenocarcinoma multidrug-resistant Colo320 cancer cells as compared to the doxorubicin-sensitive Colo205 cell line.

Crystal structure of -di-aqua-(1,4,8,11-tetra-aza-undeca-ne)nickel(II) bis-(pyridine-2,6-di-carboxyl-ato)nickel(II).

The asymmetric unit of the title compound, -di-aqua-(1,4,8,11-tetra-aza-undecane-κ , , , )nickel(II) bis-(pyridine-2,6-di-carboxyl-ato-κ ,, )nickel(II) {[Ni()(HO)][Ni(pdc)] where = 1,4,8,11-tetra-aza-undecane (CHN) and pdc = the dianion of pyridine-2,6-di-carb-oxy-lic acid (CHNO )} consists of an [Ni()(HO)] complex cation and a [Ni(pdc)] anion. The metal ion in the cation is coordinated by the four N atoms of the tetra-amine ligand and the mutually O atoms of the water mol-ecules in a tetra-gonally elongated octa-hedral geometry with the average equatorial Ni-N bond length slightly shorter than the average axial Ni-O bond [2.087 (4) 2.

The first structural characterization of the proton-ated aza-cyclam ligand in -poly[[[(perchlorato)copper(II)]-μ-3-(3-carb-oxy-prop-yl)-1,5,8,12-tetra-aza-3-azonia-cyclo-tetra-deca-ne] bis-(per-chlorate)].

The asymmetric unit of the title com-pound, -poly[[[(perchlorato-κ)copper(II)]-μ-3-(3-carb-oxy-prop-yl)-1,5,8,12-tetra-aza-3-azonia-cyclo-tetra-decane-κ , , , ] bis-(per-chlorate)], {[Cu(CHNO)(ClO)](ClO)} , (I), consists of a macrocyclic cation, one coordinated per-chlorate anion and two per-chlorate ions as counter-anions. The metal ion is coordinated in a tetra-gonally distorted octa-hedral geometry by the four secondary N atoms of the macrocyclic ligand, the mutually O atoms of the per-chlorate anion and the carbonyl O atom of the protonated carb-oxy-lic acid group of a neighbouring cation. The average equatorial Cu-N bond lengths [2.

Crystal structures of -di-aqua-(3--1,3,5,8,12-penta-aza-cyclo-tetra-deca-ne)copper(II) isophthalate hydrates ( = benzyl or pyridin-3-ylmethyl).

The asymmetric units of the title compounds, -di-aqua-(3-benzyl-1,3,5,8,12-penta-aza-cyclo-tetra-decane-κ , , , )copper(II) isophthalate monohydrate, [Cu(CHN)(HO)](CHO)·HO, (I), and -di-aqua-[3-(pyridin-3-ylmeth-yl)-1,3,5,8,12-penta-aza-cyclo-tetra-decane-κ , , , ]copper(II) iso-phthalate 0.9-hydrate, [Cu(CHN)(HO)](CHO)·0.9HO, (II) consist of one di-aqua macrocyclic cation, one di-carboxyl-ate anion and uncoordinated water mol-ecule(s).

Novel latonduine derived proligands and their copper(ii) complexes show cytotoxicity in the nanomolar range in human colon adenocarcinoma cells and in vitro cancer selectivity.

Four Schiff bases derived from 7-hydrazin-yl-5,8-dihydroindolo[2,3-d][2]benzazepin-(6H)-one and its bromo-substituted analogue (HL1-HL4) and four copper(ii) complexes 1-4 have been synthesised and fully characterised by standard spectroscopic methods (1H and 13C NMR, UV-vis), ESI mass spectrometry, single crystal X-ray diffraction and spectroelectrochemistry. In addition, two previously reported complexes with paullone ligands 5 and 6 were prepared and studied for comparison reasons. The CuII ion in 1-4 is five-coordinate and adopts a square-pyramidal or slightly distorted square-pyramidal coordination geometry.

Crystal structure of -di-aqua-(3,10-dimethyl-1,3,5,8,10,12-hexa-aza-cyclo-tetra-deca-ne)copper(II) pamoate.

The asymmetric unit of the title compound, -di-aqua-(3,10-dimethyl-1,3,5,8,10,12-hexa-aza-cyclo-tetra-decane-κ , , , )copper(II) 4,4'-methyl-ene-bis(3-hy-droxy-naphthalene-2-carboxyl-ate), [Cu(CHN)(HO)](CHO) {[Cu()(HO)](pam), where = 3,10-dimethyl-1,3,5,8,10,12-hexa-aza-cyclo-tetra-decane and pam = dianion of pamoic acid} consists of two independent halves of the [Cu()(HO)] cation and one di-carboxyl-ate anion. The Cu atoms, lying on inversion centres, are coordinated by the four secondary N atoms of the macrocyclic ligands and the mutually O atoms of the water mol-ecules in a tetra-gonally elongated octa-hedral geometry. The average equatorial Cu-N bond length is significantly shorter than the average axial Cu-O bond length [2.

Copper(ii) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells.

A series of water-soluble sodium salts of 3-formyl-4-hydroxybenzenesulfonic acid thiosemicarbazones (or sodium 5-sulfonate-salicylaldehyde thiosemicarbazones) containing different substituents at the terminal nitrogen atom (H, Me, Et, Ph) and their copper(ii) complexes have been prepared and characterised by elemental analysis, spectroscopic techniques (IR, UV-vis, H NMR), ESI mass spectrometry, X-ray crystallography and cyclic voltammetry. The proligands and their copper(ii) complexes exhibit moderate water solubility and good stability in aqueous environment, determined by investigating their proton dissociation and complex formation equilibria. The copper(ii) complexes showed moderate anticancer activity in established human cancer cell lines, while the proligands were devoid of cytotoxicity.

An iron(iii)-centred ferric wheel Fe⊂{Fe} with a siloxane-based bis-salicylidene Schiff base.

A new iron(iii)-centred ferric wheel Fe⊂{Fe} of the formula [Fe(HL)(NCS)](ClO)·10HO, where HL = N,N'-bis(3-carboxylsalicylidene)-1,3-bis(3-aminopropyl)tetramethyldisiloxane, was synthesised and fully characterised. Fe Mössbauer spectra indicate the presence of high spin (S = 5/2) Fe cations adopting a slightly different coordination environment in agreement with the X-ray diffraction structure. There are competing antiferromagnetic exchange interactions along the rim (J = -1.

A highly cytotoxic modified paullone ligand bearing a TEMPO free-radical unit and its copper(II) complex as potential hR2 RNR inhibitors.

A new paullone-TEMPO conjugate and its copper(II) complex inhibit RNR activity and show high antiproliferative activity in human cancer cell lines.

Ruthenium- and osmium-arene-based paullones bearing a TEMPO free-radical unit as potential anticancer drugs.

A modified paullone ligand bearing a TEMPO free-radical unit (HL) and its ruthenium(II) and osmium(II)-arene complexes [M(p-cymene)(HL)Cl]Cl·nH(2)O (M = Ru, Os) exhibit high antiproliferative activity in human cancer cell lines.

Reactions of potent antitumor complex trans-[Ru(III)Cl4(indazole)2]- with a DNA-relevant nucleobase and thioethers: insight into biological action.

Reactions of the complex trans-[RuCl(4)(Hind)(2)](-) (Hind = indazole), which is of clinical relevance today, with both the DNA model nucleobase 9-methyladenine (made) and the thioethers R(2)S (R = Me, Et), as models of the methionine residue in biological molecules possibly acting as nitrogen-competing sulfur-donor ligands for ruthenium atom, have been investigated to get insight into details of mechanism leading to antitumor activity. Three novel ruthenium complexes, viz., [Ru(III)Cl(3)(Hind)(2)(made)], 1, [Ru(II)Cl(2)(Hind)(2)(Me(2)S)(2)], 2, and [Ru(II)Cl(2)(Hind)(2)(Et(2)S)(2)], 3, have been isolated as solids.

Synthesis, X-ray diffraction structures, spectroscopic properties, and in vitro antitumor activity of isomeric (1H-1,2,4-triazole)Ru(III) complexes.

Three ruthenium(III) complexes containing 1H-1,2,4-triazole (Htrz), viz., (H(2)trz)[cis-RuCl(4)(Htrz)(2)], 1, (H(2)trz)[trans-RuCl(4)(Htrz)(2)], 2, and (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(2)], 3, have been synthesized by reaction between RuCl(3) and excess of the triazole in 2.38 M HCl (1 and 2), while 3 was obtained by metathesis of 2 and [Ph(3)PCH(2)Ph]Cl in water.

Synthesis, structure, spectroscopic and in vitro antitumour studies of a novel gallium(III) complex with 2-acetylpyridine (4)N-dimethylthiosemicarbazone.

The reaction of 2-acetylpyridine 4N-dimethylthiosemicarbazone (HL) with GaCl(3) in absolute ethanol in 1:1 molar ratio yielded the complex [GaL(2)][GaCl(4)]. The crystal structure of the gallium(III) complex has been determined by X-ray diffraction methods. Infrared, electronic, ESI mass and (1)H, (13)C, (15)N and (71)Ga NMR spectra, as well as the thermal behaviour are reported.