2-(4-Chloro­phen­yl)naphtho­[1,8-de][1,3,2]diaza­borinane

The title compound, C16H12BClN2, is one in a series of diaza­borinanes, derived from 1,8-diaminona­phthalene, featuring substitution at the 1, 2 and 3 positions in the nitro­gen-boron heterocycle. The structure deviates from planarity, the torsion angle subtended by the p-chloro­phenyl ring relative to the nitro­gen–boron heterocycle being −44-.3(3)°. The mol­ecules form infinite chains with strong inter­actions between the vacant pz orbital of the B atom and the π-system of an adjacent mol­ecule. The distance between the B atom and the 10-atom centroid of an adjacent naphthalene ring is 3.381 (4) Å. One N-H H atom is weakly hydrogen bonded to the Cl atom of an adjacent mol­ecule. This combination of inter­molecular inter­actions leads to the formation of an infinite two-dimensional network perpendic­ular to the c axis

2-Phenyl­naphtho­[1,8-de][1,3,2]diaza­borinane

The title compound, C16H13BN2, is one compound in a series of diaza­borinanes featuring substitution at the 1, 2 and 3 positions in the nitro­gen–boron heterocycle. The title compound is slightly distorted from planarity, with a dihedral angle of 9.0 (5)° between the mean planes of the naphthalene system and the benzene ring. The m-carbon atom of the benzene ring exhibits the greatest deviation of 0.164 (2) Å from the 19-atom mean plane defined by all non-H atoms. The two N—B—C—C torsion angles are 6.0 (3) and 5.6 (3)°. In the crystal, mol­ecules are linked by π–π inter­actions into columns, with a distance of 3.92 (3) Å between the naphthalene ring centroids. Adjacent π-stacked columns, co-linear with the b-axis, are linked by C—H⋯π inter­actions

2-[4-(Methyl­sulfan­yl)phen­yl]naphtho[1,8-de][1,3,2]diaza­borinane

The title compound, C17H15BN2S, is one member in a series of diaza­borinanes featuring substitution at the 1-, 2- and 3-positions in the nitro­gen–boron heterocycle. The dihedral angle between the mean planes of the naphthalene and phenyl ring systems is 19.86 (6)°. In the crystal structure, two C—H⋯π inter­actions link the mol­ecules into sheets which lie parallel to the bc plane. There is a π–π inter­action between each pair of centrosymmetrically related sheets [centroid–centroid distance = 3.5922 (8) Å]

A cytotoxic bis(1,2,3-triazol-5-ylidene)carbazolide gold(III) complex targets DNA by partial intercalation

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis (aryl) analogue afforded a bis(carbene) AuI -CNC pincer complex suitable for oxidation to the redox-stable [AuIII(CNC) Cl]+ cation. Although the ligand salt and the [AuIII(CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII(CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic πtype interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O···Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.https://chemistry-europe.onlinelibrary.wiley.com/journal/15213765pm2021ChemistryPhysiolog

Solution Conformations of Curcumin in DMSO

NAMFIS (<i>N</i>MR <i>A</i>nalysis of <i>M</i>olecular <i>F</i>lexibility <i>I</i>n <i>S</i>olution) has been applied to curcumin dissolved in DMSO. Quantitative ¹H–¹H distance constraints reduce a pool of candidate conformations to a solution collection of four enol conformationstwo of these match curcumin crystallized with human transthyretin, and one is closely related to a single-crystal structure of curcumin

Evidence For Inhibition Of Topoisomerase 1A By Gold(Iii) Macrocycles And Chelates Targeting Mycobacterium Tuberculosis And Mycobacterium Abscessus

Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M. abscessus call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against M. abscessus and M. tuberculosis. We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating in vitro conditions. We chose one of these hits, compound 14, for detailed analysis due to its potent bactericidal mode of inhibition and scalable synthesis. The clinical relevance of this compound was demonstrated by its ability to inhibit a panel of diverse M. tuberculosis and M. abscessus clinical isolates. Prompted by previous data suggesting that compound 14 may target topoisomerase/gyrase enzymes, we demonstrated that it lacked cross-resistance with fluoroquinolones, which target the M. tuberculosis gyrase. In vitro enzyme assays confirmed the potent activity of compound 14 against bacterial topoisomerase 1A (Topo1) enzymes but not gyrase. Novel scaffolds like compound 14 with potent, selective bactericidal activity against M. tuberculosis and M. abscessus that act on validated but underexploited targets like Topo1 represent a promising starting point for the development of novel therapeutics for infections by pathogenic mycobacteria

Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting \u3cem\u3eMycobacterium tuberculosis\u3c/em\u3e and \u3cem\u3eMycobacterium abscessus\u3c/em\u3e

Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M. abscessus call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against M. abscessus and M. tuberculosis. We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating in vitro conditions. We chose one of these hits, compound 14, for detailed analysis due to its potent bactericidal mode of inhibition and scalable synthesis. The clinical relevance of this compound was demonstrated by its ability to inhibit a panel of diverse M. tuberculosis and M. abscessus clinical isolates. Prompted by previous data suggesting that compound 14 may target topoisomerase/gyrase enzymes, we demonstrated that it lacked cross-resistance with fluoroquinolones, which target the M. tuberculosis gyrase. In vitro enzyme assays confirmed the potent activity of compound 14 against bacterial topoisomerase 1A (Topo1) enzymes but not gyrase. Novel scaffolds like compound 14 with potent, selective bactericidal activity against M. tuberculosis and M. abscessus that act on validated but underexploited targets like Topo1 represent a promising starting point for the development of novel therapeutics for infections by pathogenic mycobacteria

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis (aryl) analogue afforded a bis(carbene) AuI -CNC pincer complex suitable for oxidation to the redox-stable [AuIII(CNC) Cl]+ cation. Although the ligand salt and the [AuIII(CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII(CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic πtype interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O···Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.https://chemistry-europe.onlinelibrary.wiley.com/journal/15213765pm2021ChemistryPhysiolog

Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus

and the fast-growing species are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant strains and the high level of intrinsic resistance of call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against and We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating conditions. We chose one of these hits, compound 14, for detailed analysis due to its potent bactericidal mode of inhibition and scalable synthesis. The clinical relevance of this compound was demonstrated by its ability to inhibit a panel of diverse and clinical isolates. Prompted by previous data suggesting that compound 14 may target topoisomerase/gyrase enzymes, we demonstrated that it lacked cross-resistance with fluoroquinolones, which target the gyrase. enzyme assays confirmed the potent activity of compound 14 against bacterial topoisomerase 1A (Topo1) enzymes but not gyrase. Novel scaffolds like compound 14 with potent, selective bactericidal activity against and that act on validated but underexploited targets like Topo1 represent a promising starting point for the development of novel therapeutics for infections by pathogenic mycobacteria