In Silico Interactions of Morphine Opioids with TLR4 and TRPV1 Targets

Abstract

By the importance of exploring new inhibitors or antagonists for the over-activity of each of Toll-Like Receptor 4 (TLR4) and Transient Receptor Potential Vanilloid 1 (TRPV1) targets, derivatives of morphine opioid were investigated in this work using the in silico methodology. The original morphine and three derivatives of oxymorphone, naloxone, and naltrexone were considered the parent ligands (L1-L4), and the C-3-O-Alky functionalized models were considered as functionalized ligands (L5-L8). The singular models of ligands were optimized to obtain the minimized energy structures, and molecular docking simulations were performed to examine their interactions with the targets. The optimizations indicated significant variations of the frontier electronic molecular orbital levels proposing different activities for the ligands. Next, molecular docking simulations showed that L1 (the original morphine) was at the lowest suitability of complex formation and L8 was at the highest suitability of complex formation with both TLR4 and TRPV1 targets. Consequently, optimizing the morphine lead compound for obtaining more suitable ligands was achieved for proposing new inhibitors or antagonists for the investigated TLR4 and TRPV1 targets. © 2022 by the authors.