Records of Natural Products

A rare isoflavone mannoside, mannodaidzein (1), along with three known isoflavones (2–4), was isolated from the culture broth of an actinomycete Saccharothrix sp.JS2. Their chemical structures were determined by 1D/2D NMR and HR(ESI)MS data analyses. Among them, only compound 2 exhibited weak anti-proliferative activity against HT1080 cells at 100 µM. The structure-activity relationship analysis revealed that modification of the C-4' hydroxyl group adversely affected cytotoxicity. Mannodaidzein (1) represents the first mannoside of flavone.

The current study was designed to investigate the chemical composition, antioxidant, enzyme inhibitory, and cytotoxic activities of Scorzonera coriacea A.Duran & Aksoy. Both organs were rich in total phenolic content, with the highest content recorded from the 70% EtOH (48.41 mg GAE/g) and aqueous (47.11 mg GAE/g) extracts of the roots. All aerial parts extracts accumulated higher total flavonoid content than their respective roots extracts, with the highest amount found in their EtOH extract (36.44 mg RE/g). Chemical analysis revealed the presence of 86 compounds belonging to organic acids, phenolic acids, flavonoids, coumarins, anthocyanins, terpenes, saponins, and fatty acids and their derivatives, with the aerial parts accumulating the highest number. The roots displayed the strongest antiradical and ion-reducing capacities. EtOH extract of both organs recorded the highest acetylcholinesterase activity (2.77 and 3.02 mg GALAE/g; p≥0.05), while that of the root showed the best butyrylcholinesterase activity (3.49 mg GALAE/g) and that of the aerial parts the best tyrosinase inhibitory (59.07 mg KAE/g). EtOAc of the root exhibited the best cytotoxicity towards the HepG2 cell line (cell viability = 29.30%), but was also toxic towards HEK293 cells (cell viability = 11.72%). In silico screening supported these findings by identifying multiple strong ligand–protein interactions. Molecular dynamics simulations further confirmed the structural stability of selected complexes. In silico profiling docked 26 phytochemicals against 14 therapeutic targets, generating 364 complexes, of which 62% showed ΔG ≤ −7.0 kcal·mol⁻¹. Binding energies ranged from −1.4 to −10.7 kcal·mol⁻¹, with PD-1–Eriodictyol-7-O-neohesperidoside the best. For metabolic enzymes, Eriodictyol-7-O-neohesperidoside yielded the top α-amylase score and Diosmetin-7-O-glucoside the top α-glucosidase score, while several flavonoids bound AChE/BChE strongly; in contrast, tyrosinase displayed poor affinity overall. 100-ns MD simulations on five top complexes indicated stable behavior for C1 and C4, whereas C2/C3/C5 showed loosening interactions over time. These findings showed that S. coriacea could be a promising source of bioactive compounds with potential therapeutic applications.

Carbazole alkaloids from Murraya koenigii exhibit diverse structural features and promising anticancer potential. This study evaluated the cytotoxic activity and structure–activity relationship (SAR) of 24 carbazole alkaloids against HL-60 and HeLa cancer celllines, alongside molecular docking studies against the anti-apoptotic protein Bcl-2 (PDB ID: 2W3L).The SAR analysis revealed that electron-donating and redox-active substituents, particularly formyl groups, significantly enhanced cytotoxicity, while dimerization generally reduced potency. Docking results showed binding energies ranging from −5.49 to −9.37 kcal/mol, with key interactions mainly involving Phe63, Asp70, Phe71, Met74, Val92,Glu95, Leu96, Asp99, Gly104, Phe109, Glu111 and Phe112 residues. Potent compounds such as mahanine (15) and murrayamine-J (18) exhibited both strong cytotoxicity (IC50 = 12.1 and 5.1 μg/mL for HL-60 and 12.8 and 7.7 μg/mL for HeLa, respectively) and favorable binding affinities (−7.66 and −7.25 kcal/mol), suggesting that Bcl-2 inhibition contributes to their activity. Conversely, murrayafolline-A (2) displayed notable cytotoxicity (IC50 = 8.5 μg/mL forHL-60 and 4.6 μg/mL forHeLa) despite only moderate predicted affinity (−5.71 kcal/mol), indicating possible alternative mechanisms of action. Similarly, bisisomahanine (24) showed the strongest predicted binding (−9.37 kcal/mol) with lowest ligand efficiency but negligible cytotoxicity, suggesting that the high binding affinity is attributed to its bulky size. Overall, this study provides supportive computational insights into the cytotoxic potential of carbazole alkaloids and highlights their predictive relevance for future mechanistic and pharmacokinetic studies.

Antileishmanial activity guided studies on the methanolic extract of the tubers of Cyclamen rohlfsianum Asch. resulted in the isolation and characterization of six saponins. All saponins were established as tri-, tetra-, and pentaglycosidic derivatives of 13β-28- epoxy-oleanane-type triterpenic sapogenols. Two of them were found to be newly described saponins, rohlfsianosides A and B. Their structures were identified as 3-O-β-{[β-Dxylopyranosyl-( 1→2)-β-D-lucopyranosyl-(1→4)]-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl}- 13β,28-epoxy-16α-hydroxy-30-acetoxy-oleanane (rohlfsianoside A), and 3-O- β-{{[β-D-xylopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→4)]-[β-D-glucopyranosyl-(1→4) ]}-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl}-protoprimulagenin A (rohlfsianoside B), respectively. Additionally, three known compounds, cyclamiretin A (3β,16α- dihydroxy-13β-28-epoxy-oleanan-30-al) glycosides; cyclaminorin, deglucocyclamin and cyclamen, and protoprimulagenin A (13β-28-epoxy-3β,16α-dihydroxy-oleanane) derivative, lysikoianoside I, were identified. The structure elucidation of the saponins was established by means of spectroscopic methods (1D and 2D NMR, HR-MS). All the saponins showed notable growth inhibitory activity against Leishmania  ropica, with IC50 values ranging from 17.5 to 21.9/mL.