Purification of plant derived molecules that modulate sphingolipid enzymes in cancer and inflammation

Student thesis: Doctoral Thesis

Abstract

There is a constant need to discover new anticancer and anti-inflammatory compounds that can be developed as medicines. Sphingosine kinase 1 (SK1) and dihydroceramide desaturase (Des1) have been demonstrated to have a key role in sphingolipid metabolism and are potential targets for anticancer/anti-inflammatory therapeutics. This study aims to screen a plant library collected during field work in Egypt and then to isolate new anticancer and anti-inflammatory compounds with activity against SK1 and/ or Des1. This aim was achieved using plant extracts tested on breast cancer cell viability, proliferation and SK1 and/or Des1 protein expression. Bio-assay guided fractionation and isolation of compounds using flash column, silica gel column chromatography and preparative TLC techniques, followed by structure elucidation using 1D and 2D spectroscopic analysis enabled identification of compounds that met the criteria above. Cell proliferation was determined using [3H]-thymidine incorporation assay. Western blotting technique was used to determine the effect of isolated compounds on the targeted enzymes SK1/Des1 as well as the apoptotic pathway (PARP). There were three major findings. First, three plant species Gomphocarpus sinaicus, Urginea maritima and Pancratium tortuosum exhibited anticancer activity. Second, narciclasine was isolated for the first time from P. tortuosum and was demonstrated to inhibit cell proliferation (p
Date of Award24 Sep 2021
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorSusan Pyne (Supervisor) & Nigel Pyne (Supervisor)

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