M ichelle C. Pérez-Ayala, RISE student Dr. Enrique Rodr í guez-Borrero , Laboratory Professor

1. Efficient Synthesis of Aza-Podophyllotoxin Derivative and In Silico Studies for Amylin Inhibition in Diabetic (Type I-II) Patients 2014 Summer Bridge Program June 8th, 2014 Michelle C. Pérez-Ayala, RISE student Dr. Enrique Rodríguez-Borrero, Laboratory Professor

2. Insulin • Food Breakdown • Food is broken down to glucose • Glucose travels via the bloodstream • Insulin Production • Produced by pancreatic beta-cells • Controls glucose production and storage • Result: we receive energy www.pre-diabetes.com Pancreas-Insulin Production

3. Diabetes Symptoms: • Lack of urine release control • Blurred vision • Increased thirst • Extreme tiredness • Slow healing of wounds and cuts • Unexplained weight loss • Genital itching http://www.bbc.co.uk/science/0/21704103

4. Diabetes in Puerto rico • Puerto Ricans had the highest percentage of people with diagnosed diabetes among the Hispanic population between 1997 and 2011 • Rated 3rd death cause in Puerto Rico after heart attacks and cancer elexpresso.com beforeitsnews.com http://www.cdc.gov/diabetes/statistics/prev/national/figbyhispanic.htm

5. 2014 American Diabetes association key statistics • More than 25 million Americans have diabetes- 8 million more than just six years ago • 26% your chances of developing diabetes if your spouse already has it • 45% your likelihood developing diabetes if you have a stressful life

6. Amylin Polypeptide • Developed by pancreatic beta-cells • It is secreted into the bloodstream with insulin • Controls rate of glucose in people without diabetes • But in people with diabetes it forms a thick compact massthat stops insulin cell production • Pramlintide will serve as Amylin www.pharmaceutical-technology.com

7. Podophylotoxin and Aza-Podophyllotoxin (AP) • Podophyllotoxin is a natural precursor for the synthesis of many cancer drugs (i.e. Etoposide, Teniposide, and Etopophos) and disease treatments • Is isolated from two endangered plant sub-species and not possible to synthesize in lab yet: www.efloras.org www.pfaf.org • Podophyllumemodi (Berberidaceae) Podophyllumpeltatum

8. Hypothesis The computational software for rendering and laboratory synthesis of Aza-Podophyllotoxin derivative will have an inhibition impact on Amylin protein, thus eradicating diabetes in patients

9. Objectives Development of Aza-Podophyllotoxin(AP) derivative for inhibition of Amylin Synthesis of AP organic molecule Use computational software that will help target the specific hit areas of AP derivative on Amylin Confirm preliminary results in laboratory and continue process with toxicology studies

10. Methodology:Molecular structures www.google.com Podophyllotoxin Aza-Podophyllotoxin (Chemaxon Marvin)

11. Methodology:Medicinal Chemistry I • Synthesis of the Aza-Podophyllotoxin derivatives • Modification in the molecular structure www.clipartbest.com

12. Methodology:In Silico studies • Render: • Chemaxon Marvin • Avogadro • In Silicotesting: • BSP-SLIM www.google.com Use computational softwares

13. Methodology:Medicinal Chemistry II • Revise preliminary results • Future work: Start with toxicology study

14. references • Age-Adjusted Percentage of Civilian, Noninstitutionalized Population with Diagnosed Diabetes, Hispanics, United States, 1997–2011. (2013, April 12).Centers for Disease Control and Prevention. Retrieved June 16, 2014, from http://www.cdc.gov/diabetes/statistics/prev/ • American Diabetes AssociationJournals. (n.d.). American Diabetes AssociationJournals. Retrieved June 16, 2014, from http://www.diabetesjournals.org/ • "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 26 June 2014. <http://www.ncbi.nlm.nih.gov/pubmed/8516954>. • "UPR Cayey - Entrada al sistema de bases de datos de la Biblioteca." UPR Cayey - Entrada al sistema de bases de datos de la Biblioteca. N.p., n.d. Web. 26 June 2014. <http://www.sciencedirect.com.uprcdb.cayey.upr.edu:2048/science/article/pii/S0891584911003492?np=y>.

15. References • "University of Michigan News Service | "Security guard" zinc is off-duty in diabetes." University of Michigan News Service | "Security guard" zinc is off-duty in diabetes. N.p., n.d. Web. 26 June 2014. <http://ns.umich.edu/new/releases/7867>. • "Diabetes symptoms." - Diabetes UK. N.p., n.d. Web. 26 June 2014. <http://www.diabetes.org.uk/Guide-to-diabetes/What-is-diabetes/Diabetes-Symptoms/>. • "pramlintide, Symlin: DrugFacts, SideEffects and Dosing." MedicineNet. N.p., n.d. Web. 4 July 2014. <http://www.medicinenet.com/pramlintide/article.html>. • "Diabetes." Amylin Agonists: A Novel Approach in the Treatment of. N.p., n.d. Web. 4 July 2014. <http://diabetes.diabetesjournals.org/ content/53/suppl_3/S233.full>. • "JDRF and AmylinPartner to Investigate Co-FormulatingTwo Hormones forTreatment of Type 1 Diabetes - JDRF: ImprovingLives. CuringType 1 Diabetes." JDRF ImprovingLivesCuringType 1 Diabetes. N.p., n.d. Web. 4 July 2014. <http://jdrf.org/press-releases/jdrf-and-amylin-partner-to-investigate-co-formulating-two-hormones-for-treatment-of-type-1-diabetes/>.

16. Thank you