Developing Chlorin/Arylaminoquinazoline Conjugates with Nanomolar Activity for Targeted Photodynamic Therapy: Design, Synthesis, SAR, and Biological Evaluation.

In this report, we developed novel chlorin/arylaminoquinazoline conjugates for targeted photodynamic therapy of cancer. The synthesized photosensitizers consisted of chlorin- metallocomplexes (Zn, In, or Pd) conjugated with arylaminoquinazoline ligands with high affinity for epidermal growth factor receptors (EGFR). Additionally, the selectivity and antitumor properties of the conjugates were investigated in the EGFR-expressing A431 human tumor cell line .

Small molecule ATM inhibitors as potential cancer therapy: a patent review (2003-present).

Introduction: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials.

Areas Covered: This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors.

Photoprocesses in Bis-Diethylamino Derivatives of 1,4- and 1,3-Distyrylbenzene.

The photoprocesses of diethylamino derivatives of 1,4- and 1,3-distyrylbenzenes in MeCN were studied using absorption, luminescence, H NMR, and laser kinetic spectroscopy. Compounds and undergo intersystem crossing to the triplet state and exhibit delayed fluorescence. It was concluded that dye radical anions and radical cations are formed upon dismutation of the triplet state in the presence of an electron donor or acceptor.

Hypervalent Sulfur Derivatives as Sulfenylating Reagents: Visible-Light-Mediated Direct Thiolation of Activated C(sp)-H Bonds with Dihalosulfuranes.

In contrast to hypervalent iodine compounds, the chemistry of their sulfur analogues has been considerably less explored. Herein, we report the direct C-H bond thiolation of electron-rich heterocycles, arenes, and 1,3-dicarbonyls by dichlorosulfuranes under mild conditions. Mechanistic studies and density functional theory calculations suggest the radical chain mechanism of the disclosed transformation.

A first-in-class β-glucuronidase responsive conjugate for selective dual targeted and photodynamic therapy of bladder cancer.

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a β-glucuronidase-responsive linker. Upon activation by β-glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells.

Dioxygen-halogen bonding exemplified by crystalline peroxosolvates of ,'-bis(haloacetyl) bispidines.

The halogen bonding in molecular crystals and supramolecular assemblies has been widely investigated. Special attention is given to the molecular structures capable of simultaneously exhibiting different types of non-covalent interactions, including conventional hydrogen bonds and halogen bonds. This paper systematically analyzes crystalline peroxosolvates of bispidine-based bis-amide derivatives, containing haloacetic acid residues, namely previously reported 1,1'-(1,5-dimethyl-3,7-diazabicyclo[3.

Corrigendum: The main protease 3CLpro of the SARS-CoV-2 virus: how to turn an enemy into a helper.

[This corrects the article DOI: 10.3389/fbioe.2023.

The main protease 3CLpro of the SARS-CoV-2 virus: how to turn an enemy into a helper.

Despite the long history of use and the knowledge of the genetics and biochemistry of , problems are still possible in obtaining a soluble form of recombinant proteins in this system. Although, soluble protein can be obtained both in the cytoplasm and in the periplasm of the bacterial cell. The latter is a priority strategy for obtaining soluble proteins.

Development of an LC-MS/MS-based method for quantification and pharmacokinetics study on SCID mice of a dehydroabietylamine-adamantylamine conjugate, a promising inhibitor of the DNA repair enzyme.

Earlier, it was found that the agent KS-389, a conjugate of dehydroabietylamine and 1-aminoadamantane, possess inhibiting activity with regard to Tdp1. It this study, LC-MS/MS-based methods of quantification of KS-389 in mice blood and several organs (brain, liver and kidney) were developed and validated. Validation of the methods was performed according to the guidelines of U.

Synthesis of ,'-Unsymmetrical 9-Amino-5,7-dimethyl-bispidines.

A new approach to the preparation of ,'-unsymmetrically substituted 9-aminobispidines through aminal bridge removal reaction has been developed, the principal feature of which is the ability to selectively functionalize all three nitrogen atoms. The intermediates of 1,3-diazaadamantane's aminal bridge removal reaction are characterized, and the mechanism of this reaction is proposed based on the analysis of their structures. Representatives of the previously unknown saturated heterocyclic 1,5,9-triazatricyclo[5.

"Stereoelectronic Deprotection of Nitrogen": Recovering Nucleophilicity with a Conformational Change.

Ureas are often thought of as "double amides" due to the obvious structural similarity of these functional groups. The main structural feature of an amide is its planarity, which is responsible for the conjugation between the nitrogen atom and carbonyl moiety and the decrease of amide nucleophilicity. Consequently, since amides are poor nucleophiles, ureas are often thought of as poor nucleophiles as well.

Preparation of Ferrocene-Terminated Dendrimers for the Thermal Decomposition of Ammonium Perchlorate.

As a common oxidizer, ammonium perchlorate (AP) is an important component in composite solid propellants (CSPs). Ferrocene (Fc)-based compounds are often selected as burning rate catalysts (BRCs) to catalyze AP decomposition owing to their excellent catalytic behavior. However, one of the drawbacks of Fc-based BRCs is migration in CSPs.

Plier Ligands for Trapping Neurotransmitters into Complexes for Sensitive Analysis by SERS Spectroscopy.

Catecholamines-dopamine, noradrenaline and adrenaline are important biomarkers of neurotransmitter metabolism, indicating neuroendocrine tumors and neurodegenerative diseases. Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique with unprecedented multiplexing capabilities. However, not all important analytes exhibit strong SERS signals on stable and robust nanostructured substrates.

Photoprocesses in Derivatives of 1,4- and 1,3-Diazadistyryldibenzenes.

Photoprocesses in 1,4-diazadistyrylbenzene () and 1,3-diazadistyrylbenzene derivative () diperchlorates in MeCN were studied by absorption, luminescence, and kinetic laser spectroscopies. For compound , -photoisomerization and intersystem crossing to a triplet state are observed. For compound , photoelectrocyclization is suggested.

Structure-Property Relationships of Dibenzylidenecyclohexanones.

A series of symmetrical dibenzylidene derivatives of cyclohexanone were synthesized with the goal of studying the physicochemical properties of cross-conjugated dienones (ketocyanine dyes). The structures of the products were established and studied by X-ray diffraction, NMR spectroscopy, and electronic spectroscopy. All products had the ,-geometry.

Bispidine Platform as a Tool for Studying Amide Configuration Stability.

In this work, the solution conformations of seventeen 3,7-diacyl bispidines were studied by means of NMR spectroscopy including VT NMR experiments. The acyl groups included alkyl, alkenyl, aryl, hetaryl, and ferrocene moieties. The presence of syn/anti-isomers and their ratios were estimated, and some reasons explaining experimental facts were formulated.

Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors.

For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro).

Novel Bispidine-Monoterpene Conjugates-Synthesis and Application as Ligands for the Catalytic Ethylation of Chalcones.

A number of new chiral bispidines containing monoterpenoid fragments have been obtained. The bispidines were studied as ligands for Ni-catalyzed addition of diethylzinc to chalcones. The conditions for chromatographic analysis by HPLC-UV were developed, in which the peaks of the enantiomers of all synthesized chiral products were separated, which made it possible to determine the enantiomeric excess of the resulting mixture.

New approach to increase the sensitivity of Tb-Eu-based luminescent thermometer.

The formation of trimetallic terbium-europium-gadolinium complexes was proposed as an approach to increase the sensitivity of the corresponding terbium-europium complexes for temperature measurement due to the suppression of multiphotonic emission. This approach results in over a 2-fold increase of the sensitivity of Eu-Tb carboxylate, which reached 5.3% K-1 in the physiological range.

Supramolecular Organogels Based on -Benzyl, -Acylbispidinols.

The acylation of unsymmetrical -benzylbispidinols in aromatic solvents without an external base led to the formation of supramolecular gels, which possess different thicknesses and degrees of stability depending on the substituents in para-positions of the benzylic group as well as on the nature of the acylating agent and of the solvent used. Structural features of the native gels as well as of their dried forms were studied by complementary techniques including Fourier-transform infrared (FTIR) and attenuated total reflection (ATR) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and small-angle X-ray scattering and diffraction (SAXS). Structures of the key crystalline compounds were established by X-ray diffraction.

Isonitriles as Stereoelectronic Chameleons: The Donor-Acceptor Dichotomy in Radical Additions.

Radical addition to isonitriles (isocyanides) starts and continues all the way to the transition state (TS) mostly as a simple addition to a polarized π-bond. Only after the TS has been passed, the spin density moves to the α-carbon to form the imidoyl radical, the hallmark intermediate of the 1,1-addition-mediated cascades. Addition of alkyl, aryl, heteroatom-substituted, and heteroatom-centered radicals reveals a number of electronic, supramolecular, and conformational effects potentially useful for the practical control of isonitrile-mediated radical cascade transformations.

Crystal structures and supra-molecular features of 9,9-dimethyl-3,7-di-aza-bicyclo-[3.3.1]nonane-2,4,6,8-tetra-one, 3,7-di-aza-spiro-[bi-cyclo-[3.3.1]nonane-9,1'-cyclo-penta-ne]-2,4,6,8-tetra-one and 9-methyl-9-phenyl-3,7-di-aza-bicyclo-[3.3.1]nonane-2,4,6,8-tetra-one di-methyl-formamide monosolvate.

Compounds (I), CHNO, (II), CHNO, and (III), CHNO·CHNO represent 9,9-disubstituted-3,7-di-aza-bicyclo-[3.3.1]nonane-2,4,6,8-tetra-one deriv-atives with very similar mol-ecular geometries for the bicyclic framework: the dihedral angle between the planes of the imide groups is 74.

Crystal structure of 3-amino-pyridinium 1'-carb-oxy-ferrocene-1-carboxyl-ate.

The structure of the title salt, (CHN)[Fe(CHO)(CHO)], consists of 3-amino-pyridinium cations and 1'-carb-oxy-ferrocene-1-carboxyl-ate monoanions. The ferrocenyl moiety of the anion adopts a typical sandwich structure, with Fe-C distances in the range 2.0270 (15)-2.

Stereoelectronic Chameleons: The Donor-Acceptor Dichotomy of Functional Groups.

Stereoelectronic factors account for the apparent reversal of donor-acceptor properties of a variety of functional groups by a simple change of their orientation in space. The new reactivity patterns that arise from spatial anisotropy are associated with chameleonic behavior of common organic functionalities.