Glucopyranosylbianthrones from the Algerian <i>Asphodelus tenuifolius</i>: Structural Insights and Biological Evaluation on Melanoma Cancer Cells

Two new glucopyranosylbianthrones (<b>1</b> and <b>2</b>) were isolated from the aerial part of the plant <i>Asphodelus tenuifolius</i>, collected in Southwest Algeria. The 2D structures of <b>1</b> and <b>2</b> were defined by NMR analysis, HRESIMS data, and comparison with literature data. The comparison of experimental and calculated electronic circular dichroism and NMR data led to characterization of the (<i>M</i>) and (<i>P</i>) atropisomeric forms of the glucopyranosylbianthrones, asphodelins (<b>1</b>) and (<b>2</b>), respectively. The in vitro activities of these two metabolites were evaluated in human melanoma A375 cells, and both the compounds inhibited cell proliferation in a concentration-dependent manner, with IC₅₀ values of 20.6 ± 0.8 and 23.2 ± 1.1 μM, respectively. Considering their biological profile, an inverse virtual screening approach was employed to identify and suggest putative anticancer interacting targets

A Chemical–Biological Study Reveals C₉‑type Iridoids as Novel Heat Shock Protein 90 (Hsp90) Inhibitors

The potential of heat shock protein 90 (Hsp90) as a therapeutic target for numerous diseases has made the identification and optimization of novel Hsp90 inhibitors an emerging therapeutic strategy. A surface plasmon resonance (SPR) approach was adopted to screen some iridoids for their Hsp90 α binding capability. Twenty-four iridoid derivatives, including 13 new natural compounds, were isolated from the leaves of <i>Tabebuia argentea</i> and petioles of <i>Catalpa bignonioides</i>. Their structures were elucidated by NMR, electrospray ionization mass spectrometry, and chemical methods. By means of a panel of chemical and biological approaches, four iridoids were demonstrated to bind Hsp90 α. In particular, the dimeric iridoid argenteoside A was shown to efficiently inhibit the chaperone in biochemical and cellular assays. Our results disclose C₉-type iridoids as a novel class of Hsp90 inhibitors

Identification of 2‑Aminoacyl-1,3,4-thiadiazoles as Prostaglandin E₂ and Leukotriene Biosynthesis Inhibitors

The application of a multi-step scientific workflow revealed an unprecedented class of PGE2/leukotriene biosynthesis inhibitors with in vivo activity. Specifically, starting from a combinatorial virtual library of ∼4.2 × 105 molecules, a small set of compounds was identified for the synthesis. Among these, four novel 2-aminoacyl-1,3,4-thiadiazole derivatives (3, 6, 7, and 9) displayed marked anti-inflammatory properties in vitro by strongly inhibiting PGE2 biosynthesis, with IC50 values in the nanomolar range. The hit compounds also efficiently interfered with leukotriene biosynthesis in cell-based systems and modulated IL-6 and PGE2 biosynthesis in a lipopolysaccharide-stimulated J774A.1 macrophage cell line. The most promising compound 3 showed prominent in vivo anti-inflammatory activity in a mouse model, with efficacy comparable to that of dexamethasone, attenuating zymosan-induced leukocyte migration in mouse peritoneum with considerable modulation of the levels of typical pro-/anti-inflammatory cytokines