Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor with Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation).

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Glioblastoma (GB), a grade IV glioma, with high heterogeneity and chemoresistance, obligates a multidimensional antagonist to debilitate its competence. Considering the previous reports on thioesters as antitumor compounds, this paper investigates on use of this densely functionalized sulphur rich molecule as a potent anti-GB agent. Bio-evaluation of 12 novel compounds, containing α-thioether ketone and orthothioester functionalities, identified that five analogs exhibited better cytotoxic profile compared to standard drug cisplatin. Detailed toxicity studies of top compound were evaluated in two cell lines, using cell viability test, apoptotic activity, oxidative stress and caspase activation and RNA-sequencing analysis, to obtain a comprehensive molecular profile of drug activity. The most effective molecule presented half maximal inhibitory concentration (IC


Institute for Systems Biology