Posters
Presenting Author Academic/Professional Position
Benjamin Valdivia
Academic Level (Author 1)
Undergraduate Student
Academic Level (Author 2)
Undergraduate Student
Academic Level (Author 3)
Undergraduate Student
Academic Level (Author 4)
Faculty
Discipline/Specialty (Author 4)
Medical Education
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Immune thrombocytopenia (ITP) is a hematological disorder characterized by abnormally low platelet counts, often resulting in increased bleeding risk and impaired immune function. Current therapies may be costly, ineffective, or carry significant side effects, highlighting the need for safer, affordable alternatives. Carica papaya leaf extract has shown promise in increasing platelet counts, with flavonoids such as quercetin suggested as key bioactive constituents. However, unmodified plant compounds often suffer from limited potency or specificity. This research aims to synthesize structurally modified flavonoids derived from C. papaya to enhance their therapeutic activity for ITP. Our central hypothesis is that rational chemical modification of naturally occurring flavonoids can improve their ability to stimulate platelet production, providing a cost-effective drug discovery strategy that integrates ethnobotanical knowledge with medicinal chemistry.
Methods: We prioritized quercetin as the starting scaffold due to its synthetic accessibility and relevance in hematological studies. A six-step synthetic pathway was employed to generate a small library of quercetin analogs with modifications at key positions. Select orientin derivatives were also synthesized despite their synthetic complexity, due to their potential therapeutic activity. Compounds were evaluated using MEG-01 human megakaryoblastic cells, a model for studying platelet biogenesis. Under differentiation conditions, cells were treated with test compounds, followed by flow cytometry analysis of CD41⁺ and CD42b⁺ surface markers over 3–6 days to assess megakaryocyte maturation. This assay served as a surrogate marker for platelet-producing potential.
Results: Preliminary findings indicate that several quercetin analogs induced significant increases in CD41⁺/CD42b⁺ expression compared to untreated controls, suggesting enhanced megakaryocyte differentiation. Compounds with specific hydroxyl and methoxy substitutions at positions 3’ and 7 showed the most robust activity. Some orientin derivatives also promoted differentiation, although their yield and stability were lower. These results support the hypothesis that structural modifications can potentiate the thrombopoietic activity of plant-derived flavonoids. Advanced pathway studies and in vivo validation are planned pending additional funding.
Conclusions: Our findings demonstrate that synthetic modification of flavonoids, particularly quercetin analogs, can improve their ability to promote megakaryocyte differentiation—a critical step in platelet production. This approach presents a promising, low-cost avenue for developing novel therapeutics for ITP. Future studies will investigate molecular mechanisms of action and assess efficacy in animal models to support clinical translation.
Presentation Type
Poster
Recommended Citation
Valdivia, Benjamin; Aguilar, Alyssa; Herrera, Victoria; and Mito, Shizue, "Synthesis of various flavonoids for effective anti-immune thrombocytopenia agents" (2025). Research Colloquium. 21.
https://scholarworks.utrgv.edu/colloquium/2025/posters/21
Included in
Synthesis of various flavonoids for effective anti-immune thrombocytopenia agents
Background: Immune thrombocytopenia (ITP) is a hematological disorder characterized by abnormally low platelet counts, often resulting in increased bleeding risk and impaired immune function. Current therapies may be costly, ineffective, or carry significant side effects, highlighting the need for safer, affordable alternatives. Carica papaya leaf extract has shown promise in increasing platelet counts, with flavonoids such as quercetin suggested as key bioactive constituents. However, unmodified plant compounds often suffer from limited potency or specificity. This research aims to synthesize structurally modified flavonoids derived from C. papaya to enhance their therapeutic activity for ITP. Our central hypothesis is that rational chemical modification of naturally occurring flavonoids can improve their ability to stimulate platelet production, providing a cost-effective drug discovery strategy that integrates ethnobotanical knowledge with medicinal chemistry.
Methods: We prioritized quercetin as the starting scaffold due to its synthetic accessibility and relevance in hematological studies. A six-step synthetic pathway was employed to generate a small library of quercetin analogs with modifications at key positions. Select orientin derivatives were also synthesized despite their synthetic complexity, due to their potential therapeutic activity. Compounds were evaluated using MEG-01 human megakaryoblastic cells, a model for studying platelet biogenesis. Under differentiation conditions, cells were treated with test compounds, followed by flow cytometry analysis of CD41⁺ and CD42b⁺ surface markers over 3–6 days to assess megakaryocyte maturation. This assay served as a surrogate marker for platelet-producing potential.
Results: Preliminary findings indicate that several quercetin analogs induced significant increases in CD41⁺/CD42b⁺ expression compared to untreated controls, suggesting enhanced megakaryocyte differentiation. Compounds with specific hydroxyl and methoxy substitutions at positions 3’ and 7 showed the most robust activity. Some orientin derivatives also promoted differentiation, although their yield and stability were lower. These results support the hypothesis that structural modifications can potentiate the thrombopoietic activity of plant-derived flavonoids. Advanced pathway studies and in vivo validation are planned pending additional funding.
Conclusions: Our findings demonstrate that synthetic modification of flavonoids, particularly quercetin analogs, can improve their ability to promote megakaryocyte differentiation—a critical step in platelet production. This approach presents a promising, low-cost avenue for developing novel therapeutics for ITP. Future studies will investigate molecular mechanisms of action and assess efficacy in animal models to support clinical translation.
