Comparative Reverse Screening Approach to Identify Potential Anti-neoplastic Targets of Saffron Functional Components and Binding Mode

Abstract

<b>Background:</b> In the last two decades, pioneering research on anti-tumour activity of saffron has shed lighton the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exactmechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituentswill play an imperative role in demystifying the complex anti-neoplastic machinery. <br/><b>Methods</b>: In the quest ofpotential target identification, a dual virtual screening approach utilizing two inverse screening systems, onepredicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated withmultiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independentinverse screening platforms. The validity of the results was checked by meticulously analyzing the post-dockingbinding pose of the picrocrocin with Hsp90 alpha in AutoDock. <br/><b>Results</b>: The docking pose reveals that electrostaticand hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds tothe Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residuesinside the Hsp90-alpha ATPase catalytic site. <br/><b>Conclusion</b>: This study reveals functional information about theanti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffronhas been generated in this study which can be further authenticated by in vivo and in vitro experiments.