Progress towards the design and synthesis of novel anti-tumor neo-tanshinlactone analogues Public Deposited

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  • March 19, 2019
  • Brattlie, Joshua
    • Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
  • The goals of this research are to design and synthesize novel neo-tanshinlactone analogues utilizing bioisosterism and molecular modification, and to evaluate their bioactivity as anti-breast cancer agents. It has been shown that neo-tanshinlactone (1) and several of its analogues retain potent and selective in vitro anti- breast cancer activity. Previous research on neo-tanshinlactone focused on designing a more efficient synthetic route to synthesize 4-ethyl neo-tanshinlactone (2). This improved route was utilized to design and synthesize new compounds to elucidate structure-activity relationships (SAR) of 1. Previously designed novel analogues of 1 also revolved around the systematic breakdown of its individual rings. In this continuing study, we designed three target scaffolds (A, B, and C), and three target compounds (13, 14, and 15), based on 1 and 2 to study the effects of bioisosterism and ring size on bioactivity. Each scaffold systematically replaces a specific, and different, oxygen atom with a nitrogen atom. We have successfully synthesized two (13 and 14) target compounds, and progress has been made towards the synthesis of the third (15). Compound 13, in which the naphthalene ring system of neo-tanshinlactone has been replaced by an indole ring system, has been tested for cytotoxicity against seven cancer cell lines and has exhibited a decrease in potency and selectivity in comparison to 1 and 2.
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  • In Copyright
  • Lee, Shoou-Yih Daniel
  • Master of Science
Graduation year
  • 2014

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