Novel Quaternary Ammonium Derivatives of 4-Pyrrolidino Pyridine: Synthesis, Structural, Thermal, and Antibacterial Studies

Six novel quaternary ammonium derivatives of 4-pyrrolidino pyridine were prepared and isolated via a facile one-pot synthesis and a simple purification procedure. The purity and the molecular structure of the 4-pyrrolidino pyridine derivatives were confirmed with 1H and 13C NMR spectroscopy and powder X-ray diffraction techniques. The crystal structures of the compounds were characterized by single crystal X-ray diffraction (SCXRD) and their thermal properties were studied by Differential Scanning Calorimetry (DSC) analyses. The antibacterial properties of the title compounds against five bacterial strains were evaluated using Kirby–Bauer disk diffusion susceptibility test. The compounds crystallize in the monoclinic or orthorhombic crystal systems (space groups: P21/c, P21/n, or P212121) and their crystal structures are stabilized by a combination of intra- and intermolecular halogen bonding interactions, short contacts and π-π interactions. Above interactions, they contribute to the thermal stability and lack of phase transition effects up to 350 °C. Two of the compounds possess antibacterial effect against E. coli or S. aureus bacterial strains—similar or better than the kanamycin reference

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

The novel compound 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin is obtained in good yield via a two-step protocol; that is, initial synthesis of the reagent 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole followed by alkylation of 7-mercapto-4-methylcoumarin. The product’s structure is assigned by 1D and 2D NMR experiments and is confirmed by single-crystal XRD

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

The novel compound 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin is obtained in good yield via a two-step protocol; that is, initial synthesis of the reagent 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole followed by alkylation of 7-mercapto-4-methylcoumarin. The product’s structure is assigned by 1D and 2D NMR experiments and is confirmed by single-crystal XRD

Novel Quaternary Ammonium Aldimine Derivatives Featuring 3,4,5-Trimethoxy Phenyl Fragment: Synthesis, Crystal Structure and Evaluation of Antioxidant and Antibacterial Activity

This study demonstrates the synthesis of five novel quaternary ammonium aldimines through a two-step synthetic route involving a condensation reaction between 4-pyridincarboxyaldehyde and 3,4,5-trimethoxyaniline, followed by the quaternization of the pyridine N-atom with various aromatic α-bromo ketones. The newly obtained compounds underwent characterization for both purity and molecular structure, utilizing HR-MS, 1D, and 2D NMR spectroscopy in solution, as well as a comparison between single-crystal and powder X-ray analyses in a solid state. The thermal behavior of the studied compounds was evaluated using differential scanning calorimetry (DSC). The antioxidant properties of the compounds were assessed through DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and ferric-reducing antioxidant power (FRAP) assays, employing Trolox as a standard. The performed in vitro antibacterial screening indicates a selective antibacterial activity against Gram-negative K. pneumoniae and P. aeruginosa, while no such activity is detected for Gram-negative E. coli and Gram-positive S. aureus

Equilibrium Isotherms and Kinetic Effects during the Adsorption of Pb(II) on Titanosilicates Compared with Natural Zeolite Clinoptilolite

The present study focuses on the adsorption of Pb(II) by the H-form of titanosilicates (ETS-4, GTS-1) and clinoptilolite. The H-forms were prepared by first exchanging the extra-framework cations—Na+, K+, Ca2+, etc.—with NH4+, and by subsequent thermal treatment for obtaining H-forms. The purity and thermal behaviour of the initial, NH4+, and H-forms of ETS-4, GTS-1, and clinoptilolite were analysed by powder XRD, while the morphology and size of the particles were determined by SEM. The chemical composition of the solids and the solutions was obtained by WDXRF and ICP-OES, respectively. The kinetics research of the Pb(II) adsorption processes was based on WDXRF and ICP-OES. The H-forms of the materials displayed favourable properties for the adsorption of Pb(II). The best behaviour in this respect was demonstrated by GTS-1 when compared to ETS-4 and clinoptilolite

Polydentate <i>N</i>,<i>O</i>-Ligands Possessing Unsymmetrical Urea Fragments Attached to a <i>p</i>-Cresol Scaffold

In this study, three series of polydentate N,O-ligands possessing unsymmetrical urea fragments attached to a p-cresol scaffold are obtained, namely mono- and bi-substituted open-chain aromatics, synthesised using a common experiment, as well as fused aryloxazinones. Separate protocols for the preparation of each series are developed. It is found that in the case of open-chain compounds, the reaction output is strongly dependent on both bis-amine and carbamoyl chloride substituents, while oxazinones can be effectively obtained via a common protocol. The products are characterized via 1D and 2D NMR spectra in solution and using single-crystal XRD. A preliminary study on the coordination abilities of the products performed via ITC shows that there are no substantial interactions in the pH range of 5.0–8.5 in general

Structural Characterization of Alzheimer DNA Promoter Sequences from the Amyloid Precursor Gene in the Presence of Thioflavin T and Analogs

Understanding DNA&ndash;ligand binding interactions requires ligand screening, crystallization, and structure determination. In order to obtain insights into the amyloid peptide precursor (APP) gene&ndash;Thioflavin T (ThT) interaction, single crystals of two DNA sequences 5&prime;-GCCCACCACGGC-3&prime; (PDB 8ASK) and d(CCGGGGTACCCCGG)2 (PDB 8ASH) were grown in the presence of ThT or its analogue 2-((4-(dimethylamino)benzylidene)amino)-3,6-dimethylbenzo[d]thiazol-3-ium iodide (XRB). Both structures were solved by molecular replacement. In the case of 8ASK, the space group was H3 with unit cell dimensions of a = b = 64.49 &Aring;, c = 46.19 &Aring;. Phases were obtained using a model generated by X3DNA. The novel 12-base-pair B-DNA structure did not have extra density for the ThT ligand. The 14-base-pair A-DNA structure with bound ThT analog XRB was isomorphous with previously the obtained apo-DNA structure 5WV7 (space group was P41212 with unit cell dimensions a = b = 41.76 &Aring;, c = 88.96 &Aring;). Binding of XRB to DNA slightly changes the DNA&rsquo;s buckle parameters at the CpG regions. Comparison of the two conformations of the XRB molecule: alone and bound to DNA indicates that the binding results from the freedom of rotation of the two aromatic rings

Structural Characterization of Alzheimer DNA Promoter Sequences from the Amyloid Precursor Gene in the Presence of Thioflavin T and Analogs

Understanding DNA–ligand binding interactions requires ligand screening, crystallization, and structure determination. In order to obtain insights into the amyloid peptide precursor (APP) gene–Thioflavin T (ThT) interaction, single crystals of two DNA sequences 5′-GCCCACCACGGC-3′ (PDB 8ASK) and d(CCGGGGTACCCCGG)2 (PDB 8ASH) were grown in the presence of ThT or its analogue 2-((4-(dimethylamino)benzylidene)amino)-3,6-dimethylbenzo[d]thiazol-3-ium iodide (XRB). Both structures were solved by molecular replacement. In the case of 8ASK, the space group was H3 with unit cell dimensions of a = b = 64.49 Å, c = 46.19 Å. Phases were obtained using a model generated by X3DNA. The novel 12-base-pair B-DNA structure did not have extra density for the ThT ligand. The 14-base-pair A-DNA structure with bound ThT analog XRB was isomorphous with previously the obtained apo-DNA structure 5WV7 (space group was P41212 with unit cell dimensions a = b = 41.76 Å, c = 88.96 Å). Binding of XRB to DNA slightly changes the DNA’s buckle parameters at the CpG regions. Comparison of the two conformations of the XRB molecule: alone and bound to DNA indicates that the binding results from the freedom of rotation of the two aromatic rings

Amantadine and Rimantadine Analogues—Single-Crystal Analysis and Anti-Coronaviral Activity

In this study, we utilized the human coronavirus 229E (HCoV-229E) for evaluating the in vitro efficacy of some analogues of the ion-channel inhibitors and Amantadine and Rimantadine. The application of these investigated compounds did not result in any detectable cytotoxic effects. Furthermore, we observed that the derivatives of both analogues did not affect the viability of MDBK cells. Amantadine and Rimantadine applied at a concentration of 50 μg/mL inhibited the replication by 47% and 36%, respectively. The derivatives of Amantadine displayed a slightly weaker inhibitory effect in comparison with its own inhibitory effect. The derivative 4R of Rimantadine exhibited the same antiviral effect as the Rimantadine control, inhibiting viral replication by 37%. However, the other two derivatives of Rimantadine demonstrated lower activities. The molecular structures of the newly synthesized compounds were investigated thoroughly using single-crystal X-ray analysis. Molecular docking studies were performed using Autodock Vina. Two of the studied compounds 2A and 4A showed a promising binding affinity (−8.3 and −8.0 kcal/mol) towards SARS-CoV-2 RNA-dependent polymerase RNA site and SARS-CoV-2 Nsp3 (207-379, MES site) respectively

New Heterocyclic Combretastatin A-4 Analogs: Synthesis and Biological Activity of Styryl-2(3H)-benzothiazolones

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzothiazolone (26Z) exhibits the most potent cytotoxic activity (IC50 0.13 &plusmn; 0.01 &micro;M) against EA.hy926 cells. 26Z not only inhibits vasculogenesis but also disrupts pre-existing vasculature. 26Z is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. 26Z also shows anti-proliferative activity in CA-4 resistant cells with the following IC50 values: HT-29 (0.008 &plusmn; 0.001 &micro;M), MDA-MB-231 (1.35 &plusmn; 0.42 &micro;M), and MCF-7 (2.42 &plusmn; 0.48 &micro;M). Cell-cycle phase-specific experiments show that 26Z treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some 26Z-treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by 26Z has an exciting chemotherapeutic potential that merits further investigation