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The theoretical and infrared laser spectroscopic studies of the hydrogen chloride monomer and clusters isolated in helium nanodroplets are presented. The changes in structure due to increase of the cluster size is seen as an early stage of the structural transition to the HCl solid, which has zigzag chains of HCl molecules.

Mixed(HCl)N(H2O)Mclusters have been assembled in He droplets fromthe constituting molecules. Spectra of the clusters were obtainedin the range of hydrogen-bonded OH vibrations (3100–3700 cm–1) by infrared laser depletion spectroscopy. The observedbands were assigned to cyclic hydrogen-bonded aggregates containingup to two HCl and three H2O molecules. The obtained frequenciesare in good agreement with the results of harmonic quantum chemicalcalculations upon appropriate uniform shifts mimicking anharmoniccorrections. Although larger clusters containing up to six water moleculeswere also produced in the droplets, their spectra were found to contributeto the unresolved signal in the range 3250–3550 cm–1. The fact that no narrow bands could be unambiguously assigned tothe mixed clusters containing more than three water molecules mayindicate that such clusters exist in many isomeric forms that leadto overlapped and unresolved bands giving rise to broad structurelessfeatures. Another possible explanation includes the formation of elusivezwitterionic clusters, whose bands may have considerable breadth dueto electrostatic coupling of different vibrational modes and concomitantintramolecular vibrational relaxation. [ABSTRACT FROM AUTHOR]

Focusing on the molecular docking results, a series of 3,4-diarylisoxazoles, analogues of Combretastatin A4, bearing various substituents at the fifth position of the isoxazole ring and pharmacophore groups bioisosteric to methoxy substituent at ring B, were synthesized in good yields and high regioselectivity. Depending on the substituent at C5, three approaches were chosen for the construction of isoxazole ring, including nitrosation of gem-dihalocyclopropanes, nitrile oxide synthesis, and difluoromethoxylation of isoxazolone to afford 5-haloisoxazoles, 5-unsubstituted isoxazoles, and 5-difluoromethoxyisoxazoles, respectively. Isoxazoles 43 and 45 showed selective cytotoxicity and antitubulin inhibition properties in vitro , with pharmacodynamic profiles closely related to that of CA-4. Both of them slow down tumor growth (66-74%) in mouse xenografts and slightly exceed in effectiveness Combretastatin A4-phosphate itself., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro . In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg.

Herein, we describe the design, synthesis, and biological evaluation of novel betulin and N -acetyl-d-galactosamine (GalNAc) glycoconjugates and suggest them as targeted agents against hepatocellular carcinoma. We prepared six conjugates derived via the C-3 and C-28 positions of betulin with one or two saccharide ligands. These molecules demonstrate high affinity to the asialoglycoprotein receptor (ASGPR) of hepatocytes assessed by in silico modeling and surface plasmon resonance tests. Cytotoxicity studies in vitro revealed a bivalent conjugate with moderate activity, selectivity of action, and cytostatic properties against hepatocellular carcinoma cells HepG2. An additional investigation confirmed the specific engagement with HepG2 cells by the enhanced generation of reactive oxygen species. Stability tests demonstrated its lability to acidic media and to intracellular enzymes. Therefore, the selected bivalent conjugate represents a new potential agent targeted against hepatocellular carcinoma. Further extensive studies of the cellular uptake in vitro and the real-time microdistribution in the murine liver in vivo for fluorescent dye-labeled analogue showed its selective internalization into hepatocytes due to the presence of GalNAc ligand in comparison with reference compounds. The betulin and GalNAc glycoconjugates can therefore be considered as a new strategy for developing therapeutic agents based on natural triterpenoids.

An attractive strategy for C-Se bond formation by Ullmann-type copper(I)-promoted cross-coupling is developed. A wide range of aryliodides reacts with various disubstituted 2-selenohydantoins under mild conditions and provides Se-arylated imidazolines in moderate to high yields. Computational mechanistic studies show the oxidative addition/intramolecular reductive elimination likely to be the lowest-energy pathway. Cytotoxic activity of all 43 reaction products has been tested in vitro against MCF7 and A549 cancer cell lines with VA13 and MCF10a control cells.

A straightforward protocol toward pharmacologically relevant (het)areno[ x , y - b ]pyrrolo[1,2- d ][1,4]diazepines in good to high yields has been described. The designed approach consists of an acid-promoted furan ring opening in easily accessible N -(2-furylethyl)-2-nitroanilines or their heterocyclic analogues followed by the reductive cyclization of the corresponding nitro-1,4-diketones.

The modification of Chan-Lam-Evans cross-coupling reaction for the selective Se-arylation of 2-selenohydantoins under base-free mild conditions via aryl boronic acids is described herein. This approach was used to synthesize novel 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones with high yields. The anticancer activity of the final compounds was evaluated in vitro against different cancer cells, and thus, the possibility of 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones successful application as cytotoxic agents was demonstrated.

A simple one-pot method for the synthesis of isomeric pyrrolo[1,2- x][1,4]diazepinones in reasonable yields was developed. The method is based on the condensation of readily available N-Boc amino acids with biomass-derived furans containing aminoalkyl groups followed by deprotection, furan ring opening, and Paal-Knorr cyclization. Using this approach, we synthesized pyrrolo[1,2- a][1,4]diazepin-3(2 H)-ones from furfurylamines and β-amino acids and pyrrolo[1,2- d][1,4]diazepin-4(5 H)-ones from 2-(2-furyl)ethylamines and α-amino acids. The cytotoxicity of the synthesized pyrrolodiazepinones was studied.

We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.