Computational Investigation of Potent EGFR Inhibitors from Flavonoid-Based Phytochemical Constituents of Caralluma Europaea as Pancreatic Cancer Agents

El Khatabi, Khalil; Alaqarbeh, Marwa; Rehman, Hafiz Muzzammel; Ajana, Mohammed Aziz; Lakhlifi, Tahar; Bouachrine, Mohammed

doi:10.22036/pcr.2024.433628.2466

Computational Investigation of Potent EGFR Inhibitors from Flavonoid-Based Phytochemical Constituents of Caralluma Europaea as Pancreatic Cancer Agents

Document Type : Regular Article

Authors

khalil El khatabi ¹

Marwa Alaqarbeh ²

Hafiz Muzzammel Rehman ³

Mohammed Aziz Ajana ¹

Tahar Lakhlifi ¹

Mohammed Bouachrine ¹

¹ Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, University Moulay Ismail, Meknes, Morocco

² Basic Science Department, Prince Al Hussein bin Abdullah II Academy for Civil Protection, Al-Balqa Applied University, Al-Salt 19117, Jordan

³ School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan

https://doi.org/10.22036/pcr.2024.433628.2466

Abstract

The present study aims to identify effective bioactive compounds from Caralluma europaea as potential inhibitors of EGFR. Five Caralluma europaea compounds previously evaluated for their ability to inhibit cell proliferation were tested against EGFR and compared to the industry standard inhibitor Erlotinib. In this instance, these derivatives were focused on docking studies, which discovered the specific interactions of the identified phytocompounds with EGFR. Three phytocompounds (Hesperetin, Quercetin, and Myricetin) were shown to have the highest total scores and the best energies (lowest energy level) among compounds coming from the contribution of several interactions with EGFR. These three phytochemical compounds may have a greater inhibitory potential for the EGFR than the reference control, Erlotinib. Thus, Hesperetin was able to dock deeply within the EGFR binding region, resulting in a favorable binding interaction as well as improved total scores and docking energies, which were crucial in stabilizing the docking complex conformation. The results showed that Hesperetin had an excellent ADMET profile. The current findings forecast that the natural compound Hesperetin could be a better drug candidate for pancreatic cancer and non-small cell lung cancer, and further in vitro and in vivo studies may demonstrate its therapeutic potential.

Graphical Abstract