Computational Assessment of Chito-Oligosaccharides Interactions with Plasma Proteins

Roman, Diana Larisa; Ostafe, Vasile; Isvoran, Adriana

doi:10.3390/md19030120

Cited by 6 publications

(5 citation statements)

References 28 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structures of the protein and terpenes were prepared for docking using the “DockPrep” facility of the Chimera software [ 63 ] that was also used for analysis of the docking outputs. Molecular docking approach has also been used previously in assessing the interactions of numerous types of xenobiotics with human proteins: (i) interactions of chito-oligosaccharides with plasma proteins [ 64 ] and with the myeloid differentiation factor 2 (a protein involved in the inflammatory processes) [ 65 ]; and (ii) interactions of the stereoisomers of the fungicides triticonazole [ 50 ] and difenoconazole [ 66 ] with plasma proteins and cytochromes, respectively.…”

Section: Methodsmentioning

confidence: 99%

Predictions of the Biological Effects of Several Acyclic Monoterpenes as Chemical Constituents of Essential Oils Extracted from Plants

2023

Self Cite

View full text Add to dashboard Cite

Acyclic terpenes are biologically active natural products having applicability in medicine, pharmacy, cosmetics and other practices. Consequently, humans are exposed to these chemicals, and it is necessary to assess their pharmacokinetics profiles and possible toxicity. The present study considers a computational approach to predict both the biological and toxicological effects of nine acyclic monoterpenes: beta-myrcene, beta-ocimene, citronellal, citrolellol, citronellyl acetate, geranial, geraniol, linalool and linalyl acetate. The outcomes of the study emphasize that the investigated compounds are usually safe for humans, they do not lead to hepatotoxicity, cardiotoxicity, mutagenicity, carcinogenicity and endocrine disruption, and usually do not have an inhibitory potential against the cytochromes involved in the metabolism of xenobiotics, excepting CYP2B6. The inhibition of CYP2B6 should be further analyzed as this enzyme is involved in both the metabolism of several common drugs and in the activation of some procarcinogens. Skin and eye irritation, toxicity through respiration and skin-sensitization potential are the possible harmful effects revealed by the investigated compounds. These outcomes underline the necessity of in vivo studies regarding the pharmacokinetics and toxicological properties of acyclic monoterpenes so as to better establish the clinical relevance of their use.

show abstract

Section: Methodsmentioning

confidence: 99%

Predictions of the Biological Effects of Several Acyclic Monoterpenes as Chemical Constituents of Essential Oils Extracted from Plants

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, COs containing only GlcNAc units revealing higher interaction energies with the two proteins compared with COs containing only GlcN units, and the selectivity of the interactions was dependent on the MW, DaD and AP of COs. 9 It was also true for the interactions between the COs and human plasma proteins (alpha-1 acid glycoprotein and human serum albumin), the interacting energies increased with the molecular weight and with decreasing of deacetylation degree and were dependent on the AP. 7 In addition, a molecular docking study suggested that chitin deacetylases from fungi and marine bacteria were able to bind both totally acetylated and partially acetylated COs, but the binding energy was usually higher in the cases of the interactions with totally acetylated COs. 8 Not at last, COs with different chemical properties revealed quite distinct pharmacological profiles. 6 Results obtained using PLIP software and regarding the types of the interaction between the investigated COs and MD-2 and the amino acids involved in these interactions are presented in TABLE IV.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…5 A computational study exposed that COs, regardless of their physicochemical properties, revealed promising pharmacological profiles and few toxicological effects on humans: the inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, low potential of cardiotoxicity, and the COs with high DaD exposed the potential of producing phospholipidosis. 6 A molecular docking study revealed favorable interactions of COs with plasma proteins, the interaction energies increasing with the molecular weight (MW), decreasing with increasing DaD and being reliant on the PA. 7 Furthermore, other studies emphasized that the COs characteristics conducted to distinct affinities for chitin deacetylases 8 and lysozyme. 9 The wound healing process depends on four wound healing phases: hemostasis, inflammation, proliferation and tissue remodeling.…”

Section: Introductionmentioning

confidence: 99%

Deeper inside, the use of chitooligosaccharides, in wound healing process: A computational approach

et al. 2023

View full text Add to dashboard Cite

Chitooligosaccharides (COs) containing up to 10 monomeric units of Nacetyl D-glucosamine and/or D-glucosamine are water-soluble molecules revealing numerous biological activities and low toxicological profiles. Within this study, a computational approach has been used to predict the involvement of the COs having distinct chemical properties (molecular weight, deacetylation degree and acetylation pattern) in all the four wound healing phases: hemostasis, inflamemation, proliferation and tissue remodeling. There are predictions, for the investigated COs, regarding their molecular targets and the biological activities that are reliant to the wound healing process. Furthermore, a molecular docking approach was used to assess the interactions of the investigated COs with the myeloid differentiation factor 2 (MD-2), a protein involved in the inflammatory processes. The investigation confirms the functional roles of the investigated COs in wound healing. The molecular targets predicted for the COs containing totally and partially acetylated units are galectins and selectins and those predicted for COs containing totally deacetylated units are fibroblast growing factors, the COs containing 3 units revealing the higher number of molecular targets. All these proteins are involved in mediating immune response, inducing cell division, growth and cell adhesion during the process of wound healing. All the COs containing from 2 to 8 monomeric units are able to interact with the MD-2 protein, the interactions being stronger for the COs containing 6 and 8 monomeric units. The interaction energies increase with the increasing molecular weight and with decreasing deacetylation degree and are reliant on acetylation patterns. Among the investigated COs, the totally acetylated COs containing 6 and 8 N-acetyl glucosamine units can be better inhibitors of the LPS binding to MD-2 protein. Consequently, mixtures of COs with distinct properties should be considered suitable candidates as adjuvants in developing scaffolds for the wound healing process.

show abstract

“…To obtain this information, a computational approach was considered. In the last years, in silico methods have been used to assess the ADMET profiles and to predict the toxicological endpoints of numerous drugs and drug-related chemicals [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ], but also of other xenobiotics, such as phthalates [ 44 ], pesticides [ 12 ], artificial sweeteners [ 45 ], and industrial chemicals [ 46 ]. It emphasizes the applicability of these methods for assessing the biological activity of chemicals.…”

Section: Introductionmentioning

confidence: 99%

A Cheminformatics Study Regarding the Human Health Risks Assessment of the Stereoisomers of Difenoconazole

et al. 2022

Self Cite

View full text Add to dashboard Cite

Difenoconazole is a chemical entity containing two chiral centers and having four stereoisomers: (2R,4R)-, (2R,4S)-, (2S,4R)- and (2S,4S)-difenoconazole, the marketed product containing a mixture of these isomers. Residues of difenoconazole have been identified in many agricultural products and drinking water. A computational approach has been used to evaluate the toxicological effects of the difenoconazole stereoisomers on humans. It integrates predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles, prediction of metabolism sites, and assessment of the interactions of the difenoconazole stereoisomers with human cytochromes, nuclear receptors and plasma proteins by molecular docking. Several toxicological effects have been identified for all the difenoconazole stereoisomers: high plasma protein binding, inhibition of cytochromes, possible hepatotoxicity, neurotoxicity, mutagenicity, skin sensitization potential, moderate potential to produce endocrine disrupting effects. There were small differences in the predicted probabilities of producing various biological effects between the distinct stereoisomers of difenoconazole. Furthermore, there were significant differences between the interacting energies of the difenoconazole stereoisomers with plasma proteins and human cytochromes, the spectra of the hydrogen bonds and aromatic donor–acceptor interactions being quite distinct. Some distinguishing results have been obtained for the (2S,4S)-difenoconazole: it registered the highest value for clearance, exposed reasonable probabilities to produce cardiotoxicity and carcinogenicity and negatively affected numerous nuclear receptors.

show abstract

Computational Assessment of Chito-Oligosaccharides Interactions with Plasma Proteins

Cited by 6 publications

References 28 publications

Predictions of the Biological Effects of Several Acyclic Monoterpenes as Chemical Constituents of Essential Oils Extracted from Plants

Predictions of the Biological Effects of Several Acyclic Monoterpenes as Chemical Constituents of Essential Oils Extracted from Plants

Deeper inside, the use of chitooligosaccharides, in wound healing process: A computational approach

A Cheminformatics Study Regarding the Human Health Risks Assessment of the Stereoisomers of Difenoconazole

Contact Info

Product

Resources

About