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Daniela Andrei

Daniela Andrei

Dominican University, USA

Title: Diazeniumdiolates as HNO/NO donors: Synthesis and biological activity

Biography

Daniela Andrei earned her PhD at Florida International University in Miami, Florida and after her graduation in 2006, she worked as a postdoctoral fellow for the National Institutes of Health/National Institute of Cancer at Frederick, Maryland. She joined Dominican University in River Forest in 2008 where she serves as a full Professor of Chemistry performing research in synthetic organic and medicinal chemistry. Her research work is on nitric oxide chemistry. She has been working on the synthesis of small biological active molecules known as diazeniumdiolate or NONOates with the goal of expanding the availability of primary amine diazeniumdiolates. She has published several scientific papers in different areas of organic chemistry and is an inventor of 2 U.S. patents.

 

Abstract

Diazeniumdiolate ions, also known as NONOates, are extensively used in biochemical, physiological and pharmacological studies due to their ability to slowly release nitric oxide (NO.) and/or their congeneric nitroxyl (HNO) (Fig 1). NONOates of secondary amines have traditionally been used as NO donors and have become the standard for NO donating compounds in chemistry and biology. However, primary amine diazeniumdiolates have been less studied, and essentially IPA/NO and a few alicyclic amine diazeniumdiolates are the only representatives of this class of compounds. The purpose of this work was to synthesize a series of primary amine-based diazeniumdiolates as HNO donors and to determine their efficacy as anticancer and antifungal agents in vivo. Our compounds demonstrated a reduction in proliferation of ovarian and AML cancer cells. Similarly, they have also demonstrated some antifungal activity against various strains of Fusarium. We also used mouse RAW and human THP-1 macrophages cell line to test the compounds for anti- or pro-inflammatory properties, if any. To this end, we determined the impact of individual molecules on the LPS-induced M1 polarization and IL-4-induced M2 polarization, independently. We employed qRT-PCR and flow cytometry techniques to measure M1 and M2 phenotype after treatment with LPS or IL-4, respectively, in the absence or presence of our compounds. In order to gain an insight into the mechanism of action, we simultaneously quantified IEX-1 mRNA expression levels in response to treatment with different doses of compounds.   In conclusion, the synthesis and the biological activity of these compounds are going to be discussed in detail during the presentation.