4-Hydroxycoumarin

A series of novel 3-substituted-4-hydroxycoumarins 7 and 8 containing (5-aryl-1,3,4-oxadiazol-2-yl)thio or (4-amino-5-aryl-4H-1,2,4-triazol-3-yl)thio moieties have been synthesized and evaluated as anticancer agents. The in vitro MTT assay of compounds against hepatocellular carcinoma (HepG2), breast cancer (MCF7) cells, and a human colorectal adenocarcinoma cell line with epithelial morphology (HT29) indicated that the HepG2 cells had more susceptibility to the tested compounds. Indeed, all compounds (with the exception of 7b, 7c, 7g, and 8g) were more potent than the standard drug doxorubicin against HepG2 cells (IC50 values=1.65-3.83 μM). Although, the better result was obtained with the oxadiazole analog 7h against HepG2 (IC50 =1.65 μM), the N-amino-triazole derivatives 8c, 8e, 8f and, 8h with IC50 values of 1.78-6.34 μM showed potent activity against all tested cell lines. The good drug-like properties and in vitro potency and selectivity of 4-hydroxycoumarins 8 make them as good leads for the development of new anticancer agents.

4-hydroxyl coumarin (HC), an important intermediate during the synthesis procedure of rodenticide and anti-cardiovascular drug, shows highly medicinal value and economic value. To achieve the efficient adsorption of HC from natural biological samples, a novel magnetic surface molecularly imprinted polymer (HC/SMIPs) was constructed by employing methacrylic acid (MAA) as functional monomer, organic silane modified magnetic particles as matrix carrier and HC as template molecule. Due to the numerous specific imprinted cavities on the HC/SMIPs, the maximum adsorption capacity of HC/SMIPs for 4-hydroxycoumarin could reach to 22.78 mg g-1 within 20 min. In addition, HC/SMIPs exhibited highly selective adsorption for 4-hydroxycoumarin compared with other active drug molecules (osthole and rutin) and showed excellent regeneration performance. After 8 cycles of adsorption-desorption tests, the adsorption capacity of HC/SMIPs just slightly decreased by 6.64%. The efficient selective removal and easy recycle of 4-hydroxycoumarin from biological samples by HC/SMIPs made a highly promising to advance the application of imprinting polymers in complex practical environments.

In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.