Semi-Synthetic Analogues of Epipolythiodioxopiperazine

Primary Investigators: Nicholas Oberlies, Chiraz Soumia Amrine, Huzefa Raja

Application Number: 62/851,939

UNCG Innovation: 19-0006

Category: Chemistry & Biochemistry

Organofluorine compounds play a considerable role in drug discovery, representing about a third of all FDA­ approved drugs. Despite its abundance, comparable to that of nitrogen, the natural incorporation of fluorine into secondary metabolites is quite rare. Site directed biosynthesis is a synthetic biology approach. that expands the chemical space of privileged scaffolds to biosynthesize “unnatural natural products” that might be challenging to produce via total or semi synthesis. In this work, we generated seven new fluorinated epipolythiodioxopiperazine alkaloids. The biosynthesis of the fluorinated compounds was monitored in situ via the droplet liquid micro-junction surface sampling probe ( droplet probe), and a suite of NMR and
HRESIMS/MS/MS spectrometry data were used to characterize the new metabolites. The new derivatives and related parent compounds were tested in three types of human cancer cell lines and showed an analogous potency as the non-fluorinated analogues with IC50’s ranging from 0.04 to 0.92 µM. These compounds represent potential leads in the development of anti-cancer therapeutics.

Immediate & Future Applications:
Despite considerable advances in technology for early detection and diagnoses, cancer remains a major public health issue. As cancer progresses, or is inefficiently eliminated by current chemotherapy drugs, tumor cells often accrue mediated drug resistance. This results in making the recovery process very challenging, especially since in many cases, metastasis occurs after chemotherapy. For this reason, developing new chemical entities and new approaches to the fight against cancer is still necessary.

Inventor info: Nicholas Oberlies

Inventor info: Chiraz Soumia Amrine

Inventor Info: Huzefa Raja