Discovery of novel drug candidates based on herbaric acid derivates as potential inhibitors of the hedgehog signaling pathway in cervical cancer therapeutics

Cervical cancer ranks as the second most deadly cancer in women worldwide and as the most deadly in developing countries. However, there is currently no effective treatment for this disease. Therefore, it is necessary to find improved drugs for cervical cancer treatment. Cervical cancer is caused by human papillomavirus (HPV) infection, which has E6 and E7 proteins that may activate the Hedgehog (Hh) signaling pathway and regulate the proliferation, survival, and migration of cervical cancer cells. In this study, a novel series of herbaric acid derivates were designed and developed as potential inhibitor candidates of the Sonic hedgehog (Shh) signaling pathway. All of the potential inhibitors were analyzed and compared with Shh inhibitors, such as robotnikinin, through molecular docking simulations. Molecular docking simulations of 6310 ligands were performed using the Accelrys Discovery Studio 2.5 software according to the LibDock method. After the analysis of the ligand-Shh protein complex interaction in the docking simulation, it was found that Sd32, Sa32, and Wc34 ligands were best at inhibiting the Sonic hedgehog protein.