Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: a molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study

Abstract

Background The chemokine CXCL12 and its two receptors (CXCR4 and CXCR7) are involved in inflammation and hematopoietic cell trafficking. This study was designed to investigate molecular docking interactions of four popular cardiovascular-active natural compounds; curcumin, resveratrol, quercetin, and eucalyptol; with these receptors and to predict their drug-like properties. We hypothesize that these compounds can modify CXCL12/CXCR4/CXCR7 pathway offering benefits for coronary artery disease patients. Methods Docking analyses were carried and characterized by Molecular Environment (MOE) software. Protein Data Bank (http://www.rcsb.org/) has been retrieved from protein structure generation and crystal structures of CXCR4 and CXCR7 receptors (PDB code = 3ODU and 6K3F). The active sites of these receptors were evaluated and extracted from full protein and molecular docking protocol was done for compounds against them. The presented parameters included docking scores, ligand binding efficiency, and hydrogen bonding. The pharmacokinetic/toxic properties (ADME/T) were calculated using SwissADME, ProTox-II, and Pred-hERG softwares to predict drug-like properties of the compounds. The thermochemical and molecular orbital analysis, and molecular dynamics simulations were also done. Results All compounds showed efficient interactions with the CXCR4 and CXCR7 receptors. The docking scores toward proteins 3ODU of CXCR4 and 6K3F of CXCR7 were − 7.71 and − 7.17 for curcumin, − 5.97 and − 6.03 for quercetin, − 5.68 and − 5.49 for trans-resveratrol, and − 4.88 and − 4.70 for (1 s,4 s)-eucalyptol respectively indicating that all compounds, except quercetin, have more interactions with CXCR4 than with CXCR7. The structurally and functionally important residues in the interactive sites of docked CXCR4-complex and CXCR7-complex were identified. The ADME analysis showed that the compounds have drug-like properties. Only (1 s,4 s)-Eucalyptol has potential weak cardiotoxicity. The results of thermochemical and molecular orbital analysis and molecular dynamics simulation validated outcomes of molecular docking study. Conclusions Curcumin showed the top binding interaction against active sites of CXCR4 and CXCR7 receptors, with the best safety profile, followed by quercetin, resveratrol, and eucalyptol. All compounds demonstrated drug-like properties. Eucalyptol has promising potential because it can be used by inhalation or skin massage. To our knowledge, this is the first attempt to find binding interactions of these natural agents with CXCR4 and CXCR7 receptors and to predict their druggability.

Synthesis, Molecular Docking Study, and Cytotoxic Activity against MCF Cells of New Thiazole–Thiophene Scaffolds

“…ADME (absorption, distribution, metabolism, and excretion) studies, including drug-likeness analysis, are essential in drug discovery, and provide a reasonable decisiveness on whether or not inhibitors should be progressed to a biological system [ 31 ]. A potent antagonistic interaction of inhibitors with a receptor protein or enzyme can not guarantee the ability of an inhibitor to act as a drug; therefore, ADME assessment is essential in drug development.…”

“…The resulting Tanimoto coefficient is fingerprint-based, encoding each molecule to a fingerprint “bit” position (MACCS), with each bit recording the presence (“1”) or absence (“0”) of a fragment of the molecule. Interpretation of the probability of toxicity for compounds 4b and 13a can be explained by the cytotoxicity diagram [ 31 ].…”

“…Moreover, ADME analysis showed that the compounds have drug-like properties. ProToxII is one of the most common tools for predicting pharmacokinetic drug toxicity [ 31 ].…”

Quality Control of Oleum Cinnamomi Assisted by Network Pharmacology Strategy

“…Studies have shown that β-pinene is a bioactive compound with antioxidant, cytoprotective, and neuroprotective effects [ 22 , 23 ]. Eucalyptol, the most abundant component of Oleum Cinnamomi , has promising potential for cardiovascular disease [ 24 ]. As a strong natural antioxidant substance, p -cymene has antioxidant activities and is effective for the treatment of some severe diseases, such as cancer, diabetes, and coronary heart disease [ 25 ].…”

Halostability and thermostability of chitinase produced by fungi isolated from salt marsh soil in subtropical region of Saudi Arabia

“…A molecular modeling investigation using the Molecular Operating Environment (MOE) (Murad et al 2022;Al-Rajh et al 2022c) module was conducted to explain the observed insecticidal activity of chitinase. The structural model was built utilizing the 'BUILDER' module of MOE.…”