Investigation of Cyclobenzaprine Interactions with P450 Cytochromes CYP1A2 and CYP3A4 through Molecular Docking Tools

Abstract

Cyclobenzaprine (CBP) is a centrally acting muscle relaxant whose myriad of therapeutic applications imply the need of better understanding its pharmacokinetics and thermodynamics. Henceforth, this work was concerned with an in silico investigation of CBP main metabolizers in the human organism, namely CYP1A2 and CYP3A4. For this purpose, computational methods were employed, such as molecular docking and other semi-empirical approaches. Results evidenced that the model herein depicted for CBP-CYP1A2 may not reproducibly represent the physiological interaction between CBP and this enzyme. Moreover, CBP-CYP3A4 docking results evidence thermodynamic feasibility of the molecular docking model and were further corroborated by literature, what may reproducibly represent a possible interaction between CBP and this macromolecule.

Chemoinformatic Approaches in the Study of Fluralaner and Afoxolaner-mediated Inhibition of l-glutamate-gated Chloride Channels

“…All theoretical applications herein depicted were previously showcased in previous reports by our group [10,11].…”

“…In silico methods. The protocol herein depicted is based on previous reports by our group [10,11] in which ligands were studied concerning their kinetic and thermodynamic parameters regarding macromolecule i.e. protein/channel inhibition: FLU Moreover, the software Python Molecular Viewer (PMV) version 1.5.6 was used to evaluate torsion-prone regions in each analyzed molecule, namely: FLY and AFO, and the docking models were conducted using AutoDock Vina and Auto-Dock Tools version 1.5.6.…”

“…In this context, molecular docking strategies might provide important insights concerning the pharmacodynamics of isoxazoline ectoparasiticides. As showcased by previous reports by our group and literature, in silico tools can be applied to comprehensively assess overall physicochemical features which might foment insights about the mechanism of action of drugs [9,10,11].…”

Exploring Cheminformatic Toolsets for Predicting the Dermal Toxicity of Furanocoumarins

“…Although the exact mechanisms underlying these effects are still unclear, literature attributes to the condensed aromatic system of Psoralens pro-oxidant properties [43,44]. In this sense, some reports supported this interpretation due to the increased formation of reactive oxygen species in the presence of LF and similar compounds [19,32,[44][45][46]. Notwithstanding, the furan ring of LF also features thermodynamic feasibility to covalently bind to several biologic receptors, which could explain both the therapeutic and toxic effects of these chemicals [9,10,47,48].…”

“…This approach uses the physicochemical features of compounds converted to usable data through mono or multidimensional molecular descriptors [25][26][27][28]. This information can be correlated to databases or using data mining and machine learning algorithms to establish predictive models regarding biological activity, pharmacophores [30], docking models [27,28,31,32], and other applications. Notwithstanding, these studies can be performed on free software, i.e., freeware, for most scientific applications.…”