Design, Synthesis and Blood Vessels Sealing Activity of 2- or 4-methyl-9H-xanthen-9-one Derivatives of Aminophenols or Aromatic Chiral or Achiral Aminoalkanols.
This study explores the evaluation of 2- or 4-methyl-9H-xanthen-9-one derivatives containing aminophenols or aromatic chiral/achiral aminoalkanols as potential blood vessel-sealing agents. A series of xanthone derivatives were synthesized and evaluated through multiple bioassays, including hyaluronidase inhibition assays, antiplatelet activity via collagen-induced platelet aggregation, antioxidant potential using DPPH and FRAP assays, and vasodilatory responses in isolated rat aortic rings precontracted with phenylephrine. Among the obtained derivatives, compound 2 (2-hydroxy-N-((9-oxo-9H-xanthen-2-yl)methyl)-2-phenylethan-1-aminium chloride) demonstrated the highest hyaluronidase inhibition (19.09% at 100 μM/L), comparable to the reference compound quercetin (26.17% at 100 μM/L). Furthermore, compound 2 exhibited significant antiplatelet activity, reducing collagen-induced aggregation by 40.42% at 200 μM (p < 0.0001), similar to quercetin (40.38% at 200 μM), though weaker than acetylsalicylic acid (ASA, 71% in-hibition at 50 μM). Antioxidant studies using DPPH and FRAP assays indicated that compound 1 (4-hydroxy-N-((9-oxo-9H-xanthen-2-yl)methyl)benzenaminium chloride) surpassed vitamin C's antioxidant effect by 35%, while showing high ferric-reducing activity (91%). Additionally, compound 2 demonstrated a vasodilatory effect on rat aortic rings precontracted with phenylephrine, in contrast to quercetin, which enhanced vasoconstriction. Quercetin and α-mangostin were selected as reference compounds due to their well-established vasorelaxant mechanisms and structural similarities to the synthesized xanthone derivatives, providing a basis for comparison in evaluating vascular sealing potential and endothelial protective activity. The study's findings suggest that 2-methylxanthone derivatives, particularly compound 2, hold potential as vascular sealing agents with additional antiplatelet and vasorelaxant properties. Compound 1, based on the present study, was chosen for further research due to its significant antioxidant properties. These results warrant further pharmacological evaluation for cardiovascular applications.
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