Development of Predictive Antioxidant Models for 1,3,4-Oxadiazoles by Quantitative Structure Activity Relationship

Alisi, Ikechukwu Ogadimma; Uzairu, Adamu; Abechi, Stephen Eyije; Idris, S. O.

doi:10.18596/jotcsa.406207

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…2 none of the 33 compounds in the model are outside the range of ±3 standard deviation units. Moreover, a value of 3 for standardized residual is typically employed as a cut-off value for accepting predictions, because data that is normally distributed is covered by points that are 3 standardized residuals from the mean (46). As shown in this plot, all of the compounds' h values are less than the leverage threshold h*.…”

Section: Applicability Domainmentioning

confidence: 99%

QSAR and Drug-likeness Studies of Thiadiazole Derivatives Against Lung Cancer

Mouhsin¹

2022

YMER

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This study was aimed at building a robust quantitative structure–activity relationship (QSAR) to predict the anti-proliferate activity of 1,3,4-thiadiazole derivatives against the A549 lung cancer cell lines. The semi-empirical PM7 parametrization approach was used to optimize the complete set of 1,3,4-thiadiazole derivatives and various classes of molecular descriptors have been calculated. We built models using Fisher score and the best subset selection for feature selection, and the final model was developed using the multiple linear regression technique, all in accordance with the rigorous Organization for Economic Co-operation and Development (OECD) requirements. Furthermore, various internationally agreed severe validation parameters were used to validate the model. Overall, our established model for quick prediction should be relevant to new, untested, or not yet produced compounds that fall within the applicability domain (AD) of the model. The drug-likeness properties of the 10 compounds with the greatest activity value were also calculated using Lipinski's rule properties. Keywords: QSAR, Thiadiazole derivatives, A549, PM7, OECD

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Section: Applicability Domainmentioning

confidence: 99%

QSAR and Drug-likeness Studies of Thiadiazole Derivatives Against Lung Cancer

Mouhsin¹

2022

YMER

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“…Subsequently, their antioxidant activities were predicted using this QSAR model. In the present research, compound M04 listed in Table 1 of Alisi et al [28], whose structure is presented in Figure 1, was chosen as a template. The choice of this compound was based on its impressive antioxidant activity (pIC 50 ¼ 5.021) among the considered 1,3,4-oxadiazole antioxidant series.…”

Section: Ligand Based Virtual Screening Of 134-oxadiazole Antioxidant Derivativesmentioning

confidence: 99%

“…A set of 1,3,4oxadiazole derivatives were designed by in silico virtual screening. This was achieved by employing the recently developed quantitative structure activity relationship, (QSAR) model for 1,3,4-oxadiazole antioxidants [28]. The HAT, SET-PT and SPLET mechanisms of free radical scavenge were investigated by thermodynamic studies in this research.…”

Section: Introductionmentioning

confidence: 99%

Free radical scavenging mechanism of 1,3,4-oxadiazole derivatives: thermodynamics of O–H and N–H bond cleavage

Alisi¹,

Uzairu

Abechi

2020

Heliyon

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The thermodynamics of free radical scavenge of 1,3,4-oxadiazole derivatives towards oxygen-centred free radicals were investigated by the density functional theory (DFT) method in the gas phase and aqueous solution. Three mechanisms of free radical scavenge namely, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) were considered. The antioxidant descriptors that characterize these mechanisms such as, bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA) and electron transfer enthalpy (ETE) were evaluated. The sequence of electron donation as predicted by the HOMO results were in good agreement with the sequence of ETE for the considered molecules at their favoured sites of free radical scavenge. The reaction Gibbs free energy for inactivation of the selected peroxyl radicals, show that 1,3,4-oxadiazole antioxidants are more efficient radical scavengers by HAT and SPLET mechanisms than SET-PT mechanism in vacuum. In aqueous solution, the SET-PT mechanism was observed to be the dominant reaction pathway.

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Molecular design of curcumin analogues with potent antioxidant properties and thermodynamic evaluation of their mechanism of free radical scavenge

Alisi¹,

Uzairu

Abechi

2020

Bull Natl Res Cent

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Background Free radical attack of cellular structures in the human system is the major cause of various forms of degenerative diseases. Consequently, recent research has been focused on the development of new antioxidants with more efficient free radical scavenging potentials. Ligand-based virtual screening was employed in the rational design of potent antioxidant derivatives of curcumin by the density functional theory method. Various antioxidant descriptors that characterize the three major mechanisms of free radical scavenge, namely, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were calculated. Also, the spin density distribution on the generated radicals and the frontier orbital distribution and energy of the studied compounds were evaluated in order to gain further insight on the reaction mechanism. The reaction Gibbs free energy for scavenging the two important peroxyl radicals (HOO· and CH3OO·) was calculated in order to evaluate the preferred mechanism of free radical scavenge by these compounds. Results The investigated compounds were able to scavenge HOO· and CH3OO· radicals by HAT and SPLET mechanisms in the gas phase and aqueous solution, based on the computed results of reaction enthalpies and Gibbs free energy. The SET-PT mechanism for these compounds was observed to be thermodynamically unfeasible in the gas phase. However, the thermodynamic feasibility of free radical scavenge by SET-PT mechanism was observed in aqueous solution. Among the investigated compounds, MCC 009 (1E,4E)-1-(3-(aminomethyl)-4-hydroxyphenyl)-5-(4-hydroxy-3-((hydroxy (methyl)amino)methyl)phenyl)penta-1,4-dien-3-one at the 19-OH position possessed the highest capacity to scavenge both HOO· and CH3OO· radicals by HAT, SET-PT, and SPLET mechanisms. The reaction Gibbs free energy of scavenging HOO· radical by this molecule in the gas phase and aqueous solution is ∆rGBDEgas = − 58.18, $$ {\Delta _r{G}_{BDE}}_{H_2O}=-73.77 $$ ∆ r G BDE H 2 O = − 73.77 , ∆rGAIPgas = 611.48, $$ {\Delta _r{G}_{AIP}}_{H_2O}=-74305.49 $$ ∆ r G AIP H 2 O = − 74305.49 , ∆rGPDEgas = − 669.66, $$ {\Delta _r{G}_{PDE}}_{H_2O}=74231.72 $$ ∆ r G PDE H 2 O = 74231.72 , ∆rGPAgas = − 271.40, $$ {\Delta _r{G}_{PA}}_{H_2O}=-73.09 $$ ∆ r G PA H 2 O = − 73.09 ,∆rGETEgas = 213.22, and $$ {\Delta _r{G}_{ETE}}_{H_2O}=-0.69 $$ ∆ r G ETE H 2 O = − 0.69 . Conclusion New set of curcumin derivatives with potent free radical scavenging properties was successfully designed, and their mechanism of free radical scavenging evaluated by thermodynamic studies. This research is a gateway to the exploitation of the considered curcumin derivatives in food chemistry and pharmacy.

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Development of Predictive Antioxidant Models for 1,3,4-Oxadiazoles by Quantitative Structure Activity Relationship

Cited by 5 publications

References 36 publications

QSAR and Drug-likeness Studies of Thiadiazole Derivatives Against Lung Cancer

QSAR and Drug-likeness Studies of Thiadiazole Derivatives Against Lung Cancer

Free radical scavenging mechanism of 1,3,4-oxadiazole derivatives: thermodynamics of O–H and N–H bond cleavage

Molecular design of curcumin analogues with potent antioxidant properties and thermodynamic evaluation of their mechanism of free radical scavenge

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