Preliminary Computational Screening of Steroi...

Preliminary Computational Screening of Steroidal Derivatives as Anti-cancer Stem Cell Agents Via Hedgehog Pathway Inhibition

Author Name : Heena Parkar, Deepali Jagdale

ABSTRACT

Cancer stem cells (CSCs) are responsible for tumor recurrence and chemo-resistance. Eliminating CSCs has been suggested as a promising approach to cure cancer. Various steroidal derivatives have been reported to inhibit CSCs by targeting the hedgehog pathway. Similarly, various chalcones and pyrazolines have been reported for the inhibition of cancer cells. Considering this and using molecular hybridization technique, twenty-six steroidal chalcones and pyrazolines were designed and screened to identify a potent inhibitor of the hedgehog pathway using AutoDock Vina on Smo receptor (PDB ID: 4JKV). Steroidal naphthyl derivatives, SC23 and SP23 exhibited the highest binding energies of -9 and -10.7 kcal/mol respectively. Ligand-protein interactions indicated the importance of steroidal carboxyl and acetyl groups for hydrogen bond formation with the Smo receptor. Moreover, the results pointed out that Ser366 exhibited potent interactions with many ligands. Results influence the further investigation on steroidal derivatives aiming to develop novel anti-CSCs agents.

Keywords: CSCs, hedgehog pathway, molecular docking,steroidal derivatives