New Spisulosine Derivative promotes robust autophagic response to cancer cells.

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ID: 79591
2020
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Abstract
Therapy resistance by evasion of apoptosis is one of the hallmarks of human cancer. Therefore, restoration of cell death by non-apoptotic mechanisms is critical to successfully overcome therapy resistance in cancer. By rational drug design approach, here we try to provide evidence that subtle changes in the chemical structure of spisulosine completely switched its cytotoxic function from apoptosis to autophagy. Our most potent molecule (26b) in a series of 16 synthesized derivatives showed robust autophagic cell death in diverse cancer cells sparing normal counterpart. Compound 26b mediated lethal autophagy induction was confirmed by formation of characteristic autophagic vacuoles, LC3 puncta formation, upregulation of signature autophagy markers like Beclin and Atg family proteins. Altogether, we have detected novel autophagy inducer small molecule which can be tested further for drug discovery research.
Reference Key
ganesher2020neweuropean Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Ganesher, Asha;Chaturvedi, Priyank;Sahai, Rohit;Meena, Sanjeev;Mitra, Kalyan;Datta, Dipak;Panda, Gautam;
Journal European journal of medicinal chemistry
Year 2020
DOI
S0223-5234(19)31168-7
URL
Keywords
resistance Chemotherapy autophagy structure-activity relationship sphingoid

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