Synthesis and Cytotoxic Activity Evaluation of Gypsogenin and Hetero-Substituted Quinone Derivatives with Selected Amines
Project no. 25288 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>Gypsogenin aglycone is a triterpenoid natural compound belonging to the clove (Caryophyllaceae) family. One of the most common methods for obtaining gypsogenin is through the hydrolysis of <em>Gypsophila arrostii</em> roots, traditionally used in the preparation of “çöğen water” in Turkish confectionery. In recent years, natural compounds containing gypsogenin aglycone have gained attention due to their broad spectrum of biological activities, including antiviral, antitumor, anticarcinogenic, antioxidant, and anticancer effects.</p><p>In our previous TÜBİTAK 1001 and Bilateral Cooperation projects, we successfully isolated gypsogenin aglycone and synthesized several of its semi-synthetic derivatives. Particularly, the aminated derivatives exhibited notable biological activities, such as antibacterial, antifungal, and cytotoxic effects. These findings encouraged us to further focus our research on gypsogenin as a natural bioactive scaffold.</p><p>In parallel, compounds bearing a quinone moiety are also well-documented for their significant biological activities. Quinones are known to possess therapeutic properties such as herbicidal, fungicidal, and insecticidal activities. One of the key features of quinones is their capacity to undergo redox cycling, playing critical roles in biological redox reaction chains, including photosynthesis and cellular respiration. Amines reacting with quinone-based compounds yield derivatives that are biologically relevant and functionally active in various mechanistic pathways.</p><p>It is of great scientific importance to investigate the reactions of these two structurally distinct and biologically valuable natural scaffolds with selected amines under similar conditions and to evaluate their resultant bioactivities comparatively.</p><p>Within the scope of this project, the starting materials will include gypsogenin aglycone and several quinone derivatives, specifically 2,3-dichloro-1,4-naphthoquinone, 2-methyl-1,4-naphthoquinone (menadione, Vitamin K3), and 5-nitro-2,3-dichloro-1,4-naphthoquinone. These will be reacted with various biologically relevant amine compounds to generate new derivatives. The synthesized compounds will then be subjected to comparative biological activity assays, particularly focusing on anticancer potential.</p><p>Furthermore, all compounds will be evaluated through computer-assisted molecular docking studies to assess and optimize their binding affinity to cancer-specific molecular targets. This approach has the potential to lead to the identification of highly selective anticancer drug candidates. In addition, the amine-containing gypsogenin and quinone derivatives will be investigated not only for their interaction with cancer-related targets but also for their potential effects on protein targets associated with other diseases.</p><p>The data generated from this study are expected to contribute significantly to the literature and form the basis of high-impact publications in SCI-indexed journals with international collaboration and multidisciplinary contributions, with high citation potential.</p>