Search Results (3)

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a–s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a–s were achieved in moderate to good yields (40–70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a–s were condensed with acetophenone via Claisen–Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a–s in excellent yields (85–92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a–s were furnished in good yield (65–90%). Furan chalcone structural motifs 4a–s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a–s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2′,5′-dichlorophenyl)-2-furyl]-2–propen-1-one 4h with an IC₅₀ value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2′-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC₅₀ value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC₅₀ = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure–activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones. Full article

The pharmacological effects of the presence of a sugar moiety, 1,2,3-triazole ring and silyl groups in the structure of biologically active compounds have been extensively studied in drug design and medicinal chemistry. These components can be useful tools to tailoring the bioavailability of target molecules. Herein we present the study on the impact of the sugar substituent structure and triisopropylsilyl group presence on the anticancer activity of mucochloric acid (MCA) derivatives containing the furan-2(5H)-one or 2H-pyrrol-2-one core. The obtained results clearly indicated that tested compounds caused a significant decrease in cell viability of HCT116 and MCF-7 cell lines. MCF-7 cells indicate serious resistance toward investigated compounds in comparison with HCT116 cell line, it suggests that estrogen-dependent breast cancer cells are significantly less sensitive to the tested derivatives. Depending on the structure of the sugar, the type and site of connection with the furanone or 2H-pyrrol-2-one derivative and the presence of the silyl group, the selectivity of the compound towards cancer cells can be controlled. The obtained results may have an impact on the design of new furanone-based anticancer compounds. Full article

Human protein kinase CK2 is an emerging target for neoplastic diseases. Potent lead structures for human CK2 inhibitors are derived from dibenzofuranones. Two new derivatives, 7,9-dichloro-1,2-dihydro-8-hydroxy-4-[(4-methoxyphenylamino)-methylene]dibenzo[b,d]furan-3(2H)-one (4a) and (E)-1,3-dichloro-6-[(4-methoxyphenylimino)-methyl]dibenzo[b,d]furan-2,7-diol (5) were tested for inhibition of CK2 and induction of apoptosis in LNCaP cells. Both turned out to be tight binding inhibitors, with IC₅₀ values of 7 nM (4a) and 5 nM (5) and an apparent K_i value of 0.4 nM for both. Compounds 4a and 5 reduced cellular CK2 activity, indicating cell permeability. Cell viability was substantially impaired in LNCaP cells, as well as apoptosis was induced, which was not appearing in non-neoplastic ARPE-19 cells. Co-crystallization of 4a and 5 revealed an unexpected π-halogen bond of the chloro substituent at C9 with the gatekeeper amino acid Phe113, leading to an inverted binding mode in comparison to parent compound 4b, with the Cl at C6 instead, which was co-crystallized as a control. This indicates that the position of the chloro substituent on ring A of the dibenzofuran scaffold is responsible for an inversion of the binding mode that enhances potency. Full article