• Arif Jamal Siddiqui, Mohammad Faheem Khan, Walid Sabri Hamadou, Manish Goyal, Sadaf Jahan, Arshad Jamal, Syed Amir Ashraf, Pankaj Sharma, Manojkumar Sachidanandan, Riadh Badraoui, Kundan Kumar Chaubey, Mejdi Snoussi, and Mohd Adnan.
• Department of Biology, College of Science, University of Hail, Hail 2440, Saudi Arabia.
• Medicina (Kaunas). 2021 Oct 3; 57 (10).

AbstractUrogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

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