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oai:figshare.com:article/32995349 2026-05-01T00:00:00Z portal_693 item_type_8 month_year_05_2026

Drug Discovery in Redox Biology: From Natural Products to Structural Biology Peculiar Feenna Onyekere (24400289) Chemistry Biochemistry Redox-regulating systems play essential roles in maintaining cellular homeostasis and represent important therapeutic targets in cancer and infectious diseases. Natural products provide structurally diverse redox-active scaffolds capable of modulating oxidative stress and redox sensitive signaling pathways. The genus Rinorea (Violaceae) is metabolically diverse yet remains largely underexplored. Rinorea longiracemosa (Kurz) Craib, traditionally used in Laos for inflammatory conditions, has received limited phytochemical and pharmacological investigation. To address this gap, a bioassay-guided isolation approach was employed to evaluate the cytotoxic potential of R. longiracemosa stem bark extracts against prostate cancer (22Rv1) cells. Sequential chromatographic fractionation followed by semi-preparative HPLC purification yielded six compounds identified by spectroscopic analysis as vanillin, propylene glycol, β hydroxypropiovanillone, 1,4-bis(2-hydroxyethoxy)benzene, evofolin B, and (+)-syringaresinol. Among these, 1,4-bis(2-hydroxyethoxy) benzene and (+)-syringaresinol exhibited moderate cytotoxic activity against OVCAR3 cells (IC₅₀ = 100 µM), while 1,4-bis(2 hydroxyethoxy)benzene also showed activity against MDA-MB-435 cells. These phenolic scaffolds represent potential redox-active anticancer leads. To complement natural product discovery with structural insight, thioredoxin glutathione reductase (SmTGR), a key enzyme in parasite redox homeostasis, was purified and crystallized. SDS-PAGE and UV–Visible spectroscopy confirmed protein purity and FAD incorporation. Crystals obtained via hanging-drop vapor diffusion diffracted to ~4.0 Å at the Advanced Photon Source, enabling visualization of the enzyme’s overall fold and catalytic redox center, supporting structure-guided inhibitor development. 2026-05-01T00:00:00Z Text Thesis 10.25417/uic.32995349.v1 https://figshare.com/articles/thesis/Drug_Discovery_in_Redox_Biology_From_Natural_Products_to_Structural_Biology/32995349 In Copyright Open Access after 2028-05-01