Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.

Compounds bearing [1,3]dioxolo‐quinoline scaffolds have been found in quinoline‐based natural products; the only exception is the [1,3]dioxolo[4,5‐c]quinoline moiety with a rare occurrence in both natural and synthetic derivatives. In this article, we report the preparation of diversely substituted and functionalized [1,3]dioxolo[4,5‐c]quinolines using [1,3]dioxolo[4,5‐c]quinoline‐4‐carbaldehyde (DQC) as the common intermediate. DQC was synthesized on a large scale from anthranilic acid and chloroacetone as the starting materials, with the rearrangement of acetonyl‐anthranilate as the key step. The developed method allows for the simple preparation of [1,3]dioxolo[4,5‐c]quinolines with various C2 substituents on the quinoline scaffold. Additionally, the synthetic route was successfully applied to the preparation of 3‐hydroxyquinoline‐4(1H)‐ones. The target compounds were tested against representative Gram‐positive/negative bacteria, and two derivatives exhibited submicromolar minimum inhibitory concentrations against Micrococcus luteus.

We have synthesized a series of 2-phenyl-3-hydroxy-4(1H)-quinolinone derivatives substituted with one or more fluorine atoms on the quinolone backbone as well as on phenyl ring. The derivatives bearing more fluorine atoms were subjected to modification by nucleophilic substitutions by thiophenol, morpholine, and piperazine derivative. We have tested the prepared compounds in cytotoxic activity assay against cancer cell lines. Four derivatives exhibited micromolar values of IC50 against some of the cancer cell lines, and we have subjected them to cell cycle analysis on CCRF-CEM. Moreover, most active 7-fluoro-3-hydroxy-2-phenyl-6-(phenylthio)quinolin-4(1H)-one inhibits mitosis progression. Cell cycle analysis, in vitro tubulin polymerization assay, and tubulin imaging in cells indicated that the anticancer activity of thiophenol derivative is associated with its ability to inhibit microtubule formation.

In this work, we report the simple synthesis of furo[3,2-b]quinolin-4(1H)-ones from readily available 4-ethynyl-[1,3]dioxolo[4,5-c]quinolone as the key starting material. After Sonogashira (hetero)arylation, formation of the furoquinoline scaffold was accomplished using methanesulfonic acid and metal-free conditions. Although the cyclization was affected by the substitution of reaction intermediates, the method allowed the preparation of derivatives varying at the C3-position.

Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

A synthetic approach to novel 2-(1-glycosyl-1,2,3-triazol-4-yl)-3-hydroxyquinolone conjugates has been developed. The methodology involves preparation of a suitable quinoline intermediate and its subsequent conjugation with various acylated glycosyl azides by CuAAC click reaction. A choice of protective group at quinoline moiety appeared to be crucial for subsequent 3-step deprotection sequence that has to kept glycosyl triazole bond intact. Evaluation of antimicrobial properties of the conjugates revealed that their activity was strongly affected by protecting group of the quinoline moiety. Some of the conjugates inhibited exclusively G+ bacterial strains including honeybee larval pathogen Paenibacillus larvae, which were most susceptible to 2-substituted, particularly 2-glycosylated, dibenzylated quinolines.

In this work, we attempted to synthesize thioflavonols using rearrangement of phenacyl thiosalicylates prepared by two different approaches and subjected to cyclization under acidic conditions. Contrary to our expectations, the isolated products were identified as (3-hydroxybenzo[b]thiophen-2-yl)(phenyl)methanones. The detailed reaction mechanism was elucidated by characterization of all reaction intermediates with HPLC and NMR spectroscopy. The applicability of the reaction using different phenacyl esters was tested.

2-Alkenyl-3-hydroxyquinolin-4(1H)-ones were prepared by the rearrangement of anthranilic acid esters synthesized by two alternative methods. The prepared derivatives were screened for their antimicrobial activities against representative Gram-positive and Gram-negative bacteria, displaying notable minimum inhibitory concentration values against specific strains. The emission spectra of the target quinolines exhibited two well-separated emission bands, and the maximum excitation wavelengths of the selected compounds were detected at relatively high values.

Na+/K+-ATPase (NKA) is an enzyme of crucial importance for all animal cells. We examined the inhibitory effects of halogenated phenylquinolinones on NKA. The 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one (TFHPQ) was identified as an efficient NKA inhibitor with IC50 near 10 μM. The inhibition by TFHPQ is particularly efficient at higher concentrations of K+, where NKA adopts the E2 conformation. The experimental observations are in a good agreement with the outcomes from molecular docking. We identified an energetically favourable TFHPQ binding site for the K+-bound NKA, which is located in the proximity of the cytoplasmic C-terminus.

A general and efficient synthesis of 4-substituted-1H-pyrazole-3,5-diamines was developed to access derivatives with an aryl, heteroaryl, or styryl group, which are otherwise relatively difficult to prepare. The first step is based on the Suzuki-Miyaura cross-coupling reaction utilizing the XPhos Pd G2 precatalyst. The coupling reactions of 4-bromo-3,5-dinitro-1H-pyrazole with the electron-rich/deficient or sterically demanding boronic acids enabled the production of the corresponding dinitropyrazoles. The subsequent iron-catalyzed reduction of both nitro groups with hydrazine hydrate accomplished the synthesis. The additional demethylation of the 4-methoxystyryl derivative allowed the production of the carboanalog of CAN508 reported as a selective CDK9 inhibitor.

In a polar environment, tris(2-chloroethyl)amine molecule undergoes isomerization when forming N,N-bis(2-chloroethyl)aziridinium cation as a reactive intermediate. New methods were developed to spectrophotometrically determine tris(2-chloroethyl)amine in the form of aziridinium cation extraction using 4 sulfonephthaleins—bromothymol blue, thymol blue, bromoxylenol blue, and bromocresol green. The developed methods, reflecting potent electrophilic properties of the analyte, are based on the formation of extractable ion pairs between the aziridinium cation and a quinoid anion form of a sulfonephthalein. Chloroform was used as the solvent for extraction from the water phase. The conditions of the methods were optimised by determining the suitable pH (8.5) of a buffer and the concentration of sulfonephthaleins as reagents. The dependence of the reaction time in the water phase was found to be 10 min. The composition of the ion pairs was found to be 1:1 by in all cases and the conditional extraction constant of the complexes were calculated. The detection and determination limits of separate procedures were ascertained. Best results (detection limit 3.5 µg ml−1 and determination limit 11.6 µg ml−1) were obtained using bromothymol blue. The methods were empirically compared with a group spectrophotometric method to determine alkyl halides using the alkalized water–ethanol solution of thymolphthalein. Relatively low interferences of other nitrogen mustards and sulfur mustard were recorded. The interaction mechanism—ion association—was validated.

A series of 2-substituted-3-diazoquinolin-4-ones is prepared by the reaction of 2-substituted-3-amino-4-chloroquinolines with sodium nitrite in sulfuric acid. Some of the obtained products are then utilised in triazole formation, reduction and a Wolff rearrangement/Friedel–Crafts ketene capture.

A procedure for the preparation of derivatives of phen­acyl hydrazonopropanoates and their application in the synthesis of various heterocycles has been developed. Not only is the preparation of indole derivatives described, but also a new method for the preparation of previously unknown pyridazine derivatives.

AbstractThe title compound (II) is easily prepared from salt (I) and coupled with various oxygen‐, sulfur‐, and nitrogen‐containing nucleophiles.