Small-scale screening program for the identification of cytotoxic Oxazolo[5,4-d]pyrimidine derivatives based on Whole Cell Viability Assay

For over last couple of decades, there has been a robust activity aimed towards the discoveryof novel anti-cancer therapeutics. An approach to identify starting points for new drugcandidates is high throughput screening of compound library collection. In this work, wedescribe the application of a Tetrazolium-based, 96-well small scale screening assay to screena mini library of 19 compounds bearing Oxazolo[5,4-d]pyrimidine structures against humanumbilical vein endothelial cells. Primary actives identified against HUVEC were retested andthe IC50 value compounds were estimated for HUVEC. The screening program (Primaryscreening) identified 4 compounds with inhibition rate percentage ≥ 70% each. Retestscreening of these compounds, taking into account criteria required for high cytotoxiccompounds, afforded a panel of 1 compound for further biological analysis. This compoundhad IC50 value of 12.19µM, 12.16µM, 10.24µM, 20.43µM for HUVECs, SGC7901, MCF7,and HeLa respectively. Furthermore, a clonogenic assay was performed in order to confirmthe cytotoxic activity of the selected compound on the survival and proliferation of MCF7.This compound was found to significantly effect the survival and proliferation of MCF7.Taken together, the selected compound, namely SCYJ32, was found to be highly cytotoxicagainst the numerous cell lines. Further studies are ongoing in order to unravel variousmechanisms of action of this novel small compound.