Adedirin Oluwaseye - Academia.edu (original) (raw)
Papers by Adedirin Oluwaseye
Preparations of the complexes Preparation of the Cu[N-FMBH]SO 4 .2H 2 O complex 2g (0.0093 mol) o... more Preparations of the complexes Preparation of the Cu[N-FMBH]SO 4 .2H 2 O complex 2g (0.0093 mol) of N-FMBH was dissolved in 150 ml absolute ethanol and 2.33g (0.0093 mol) of CuSO 4 .5H 2 O was dissolved in 25 ml of distilled deionized water. The N-FMBH solution was then poured gently into the metal ion Abstract N'((furan-2-yl) methylene) benzohydrazide (N-FMBH) and 2-(2-aminothiazol-4-yl) acetohydrazide (2-ATCH) were prepared and characterized by melting point and infra-red studies. Their complexes with some M(II) sulphates (M = Mn, Co, Ni and Cu) were synthesized and characterized by melting point, solubility, infra-red and electronic spectral studies. The ligands are mainly neutral bidentate donors ligating via the carbonyl O and the primary amino N (or the azomethine N in the case of N-FMBH). The nickel, manganese and cobalt complexes are octahedral while the copper complexes are square planar respectively. The ligands and complexes showed some activity against Bacillus subtilis, Staphlyococus aureus, Escherichia coli and Klebseila pneumonia.
Quantitative structure-activity relationship study was done on 62 compounds with anticonvulsant a... more Quantitative structure-activity relationship study was done on 62 compounds with anticonvulsant activity in maximal electroshock-induced seizures test. The molecular structure of the compounds was optimized with parametric semi-empirical PM3 method available in Spartan 14 software. Quantum mechanical descriptors were extracted from the property and output module of the software. Combination of activity based-clustering and genetic function algorithm chemo-metric techniques were used to map molecular descriptors to activity values. A well-validated and robust quantitative structure-activity model was obtained with R2 = 0.947, Q2= 0.924, F = 91.42 and R2pred(test) = 0.881. The descriptor contained in the model suggested an increase in the number of O and N atoms in the molecule augments the activity of the studied compounds. Also, the introduction of electron donating substituents is beneficial to the activity of the studied compounds. Armed with these, information, new hypothetical1H...
The leaves of Loranthus micranthus Linn on shear butter tree was harvested in Suleja Nigeria for ... more The leaves of Loranthus micranthus Linn on shear butter tree was harvested in Suleja Nigeria for phytochemical screening, antioxidant activities, antimicrobial properties and proximate analyses. The crude ethanol extract of L. micranthus was observed for its antimicrobial activities at various concentrations (60, 30 and 15 µg/disc) using agar diffusion method, and was tested on Staphylococcus aureus, Escherichia coli, Salmonella paratyhi-1, Klebbsiella pneumoniae, and Proteus mirabilis and the results documented. Gradient extractions of ethanol (A), petroleum-spirit (B) and ethyl acetate (C) extracts were screened for phytochemical analysis and the result for ethanol extract showed positive results for tannins, glycosides, saponins, phenols, cardiac glycosides, phlobatanins, volatile oil, steroids and balsams; petroleum spirit extract indicated positive result for tannin, phenols, alkaloids, cardenolides, terpenoids, flavonoids, carbohydrates, resins, and volatile oil. While ethyl a...
Journal of Computational Methods in Molecular Design, 2015
Quantitative Structure Property Relationship (QSPR) analysis was applied to 36 Persistent Organic... more Quantitative Structure Property Relationship (QSPR) analysis was applied to 36 Persistent Organic Pollutants (POPs) using a combination of 0D, 1D, 2D and 3D molecular descriptors obtained by Semi empirical (pm3) method. The computed descriptors were correlated with the log of their experimental octanol-air partition coefficient (pKOA).Genetic function approximation was used to derive the most statistically significant QSPR model as a calibration model for predicting the pKOA of this class of molecules. Among the obtained QSPR models, the most statistically significant one was a five parameter linear equation with the squared correlation coefficient R2 value of 0.9889, adjusted squared correlation coefficient R2adj value of 0.9860 and Leave one out (LOO) cross validation coefficient (Q2) value of 0.9827. An external set was used for confirming the predictive power of the model (R2pred. = 0.7471). It is envisaged that the QSPR results identified in this study will offer an efficient a...
Journal of King Saud University - Science, 2018
Quantitative structure-activity relationship (QSAR) and molecular docking studies have been done ... more Quantitative structure-activity relationship (QSAR) and molecular docking studies have been done on 28 isoxazole and thiazole derivatives with anticonvulsant activity in subcutaneous pentylenetetrazole animal model. Physicochemical parameters obtained from PaDEL-Descriptors were utilized in the study. Parametric semi-empirical quantum technique PM3 available in Spartan 14 program was used to optimize the molecular structure of the dataset compounds. Genetic function algorithm, Modified-K-Medoid clustering, correlation analysis and multiple linear regressions were used to search for the best QSAR model. The model obtained had good statistical parameters (LOF = 0.056, R 2 = 0.975, Q 2 = 0.959, F 3,15 = 198.058, R 2 (Pred.) = 0.761, PRESS = 0.058, SEE = 0.062 and c R 2 P = 0.887) and can be utilized to predict the anticonvulsant activity of compounds that are within its chemical space. Molecular docking analysis showed that the studied compounds had a better binding affinity for c-aminobutyrate aminotransferase than vigabatrin which is a known inhibitor of c-aminobutyrate aminotransferase.
Journal of King Saud University - Science, 2018
Computational study was carried out to develop a Quantitative structure-activity relationship (QS... more Computational study was carried out to develop a Quantitative structure-activity relationship (QSAR) model and molecular docking studies on 4-Phenoxynicotinamide and 4-Phenoxypyrimidine-5-carboxamide derivatives as potent anti-diabetic agent. Chemical structure of these molecules were optimized with Density Functional Theory (DFT) utilizing the B3LYP with 6-31G* basis set. Five QSAR models were generated using Multi-Linear Regression and Genetic Function Approximation (GFA). Model one was selected as the optimum model and reported based on validation parameters which were found to be statistically significant with squared correlation coefficient (R 2) of 0.9460, adjusted squared correlation coefficient (R 2 adj) value of 0.9352 and cross validation coefficient () value of 0.9252. The chosen model was subjected to external validations and the model was found to have (R 2 test) of 0.8642. Molecular docking studies revealed that the binding affinities of the compounds correlate with their pEC 50 and the best compound has binding affinity of-10.4 kcal/mol which formed hydrogen bond and hydrophobic interaction and with amino acid residues of TGR5 receptor. QSAR model generated and molecular docking results propose the direction for the design of new anti-diabetic agent with better activity against TGR5 target site.
Journal of King Saud University - Science, 2018
DFT quantum mechanical method B3LYP/631G ⁄⁄ was used to optimize the molecular geometry of some 2... more DFT quantum mechanical method B3LYP/631G ⁄⁄ was used to optimize the molecular geometry of some 2-amino-N-benzylacetamide derivatives with anticonvulsant activities. Molecular descriptors were extracted from the optimized structure and used together with their activity as the database for the study. Kennard-Stone algorithm, genetic function algorithm, and multiple linear regressions were used to build a robust quantitative structure-activity relationship model. The quality of the model was shown by its parameters: R 2 (0.9270), R 2 adj (0.9178), F 8,63 (100.02), Q 2 (0.9036) and R 2 pred (0.7406). Therefore, the model can be used to predict the activity of new chemicals that within its applicability domain. The x-component of molecular dipole moment (d x), HOMO-LUMO energy gap (De), electrophilicity index (X), square of ovality (U 2), anisotropy of the polarizability (b 2), topological electronic index (T E), square root of the sum of square of charges on all hydrogen (QH) and square root of the sum of square of charges on all nitrogen (QN) are the descriptors that influenced the anticonvulsant activity of the studied compounds. This information can be utilized in the future to optimize the anticonvulsant activity of the studied compounds.
Beni-Suef University Journal of Basic and Applied Sciences, 2018
Chemometric descriptors were used to analyze quantitatively the anticonvulsant activity of ninety... more Chemometric descriptors were used to analyze quantitatively the anticonvulsant activity of ninety propanamide derivatives. Molecular geometries of the data set were optimized with B3LYP/6-31G * * quantum mechanical method and chemometric descriptors were calculated from the optimized structure. Linear QSAR models were developed using genetic function algorithm. Predictive capabilities of the models were evaluated using various internal and external validation techniques. The best three models proposed were octa-parametric equation with good statistical quality: R 2 (0.898-0.918); Q 2 (0.865-0.893); R 2 pred (0.746-0.772) and F (66.657-88.036). 2acetamido-N-benzyl-2-(5-methylfuran-2-yl) acetamide a member of the data set was chosen as scaffold for in silico design. Using the information afforded by the models, several attempts were made to optimize the scaffold by introducing various modifications. Potential derivatives with higher predicted activity values than the template were identified and a detailed analysis on the models applicability domain defined the designed compounds, whose estimations can be accepted with confidence. Some of the designed compounds docked with γ-aminobutyrate aminotransferase (PBD: 1OHV) (target) showed better binding affinity for the target when compare with 4-aminohex-5-enoic acid (vigabatrin) (a known inhibitor of the target).
The Journal of Engineering and Exact Sciences, 2018
Quantitative structure activity relationship study (QSAR) and molecular docking were used to desi... more Quantitative structure activity relationship study (QSAR) and molecular docking were used to design and virtually screen some new N-benzylacetamide derivatives for their ability to inhibit ?-amino butyrate-aminotransferase. Ninety compounds with anticonvulsant activity against maximal electroshock induced seizures were used for QSAR study. B3LYP/6-31G** quantum mechanical method was employed to optimize/minimize the molecular structure of these compounds. Genetic Function Algorithm (GFA) method was used to develop the QSAR models. Each model gave an octa-parametric equation with good statistical qualities (R2 ranged from 0.823 to 0.893, Q2 from 0.772 to 0.854, F from 36.53 to 37.10, R2pred(test) from 0.768 to 0.893). Information obtained from the parameter contained in the model suggested that increasing the molecular mass and linearity of molecule would lead to increase in anticonvulsant activity of studied compounds. These informed the design and virtual screening of 118 new N-ben...
Beni-Suef University Journal of Basic and Applied Sciences, 2018
Computational methods were used to study the structural parameters that influence that anticonvul... more Computational methods were used to study the structural parameters that influence that anticonvulsant activity of some α-aminoacetamides which were active in maximal electroshock seizure test. Their molecular structures were optimized with B3LYP/631G** density function theory method using Spartan 14 software. Modified-Kmediod clustering algorithm was used for data division, genetic function algorithm was used for variable selection and multiple linear regressions method was used for model construction. Developed model was statistically significant with coefficient of determination (R 2) of 0.957, cross-validated R 2 i.e. Q 2 of 0.927, variance ratio (F 4,15) of 82.94, Y-randomization R 2 i.e. c R 2 P of 0.840 and predicted R 2 (R 2 Pred) of 0.812. The molecular descriptors contained in the model were GATS8c (Geary autocorrelation of lag-8/weighted by atomic charges); VCH-7 (valence chain of order 7); VE3_D (Logarithmic coefficient sum of the last eigenvector from topological distance matrix) and RDF100p (radial distribution function − 100/weighted by polarizability). Molecular docking result showed that studied compounds had high binding affinity for neuronal sodium channel (PDB: 2KaV). Their binding affinity compared favorably with that of phenytoin, a validated sodium channel blocker. In addition, a linear relationship existed between anticonvulsant activity of studied compounds and their binding affinity for neuronal sodium channel.
Journal of the Turkish Chemical Society, Section A: Chemistry, 2017
A quantitative structure-activity relationship (QSAR) study was performed to develop a model that... more A quantitative structure-activity relationship (QSAR) study was performed to develop a model that relates the structures of 62 compounds, which have activity against maximal electroshock-induced seizure (MES), with their anti-MES activity. Molecular structures of the compounds were geometrically optimized and energetically minimized using a combination of modified Merck force field (MMFF) molecular mechanics, Austin model 1 (AM1) semi-empirical quantum mechanical and density functional theory (DFT) quantum mechanical method using the Becke's three parameter exchange functional (B3) hybrid with Lee, Yang and Parr correlation functional (LYP) and basis set of the double zeta split valence plus polarization quality 6-31G** i.e. B3LYP/6-31G**. Theoretically derived descriptors were obtained from the optimized structures, a genetic function approximation (GFA) algorithm was also applied to select the optimal descriptors and multiple linear regression (MLR) was used to establish a relationship between the anti-MES activity of the compounds and the optimal molecular descriptors. A six-parametric equation containing dipole moment (μ), energy of the lowest unoccupied molecular orbital (ϵLUMO), polar surface area (PSA), accessible surface area derived from wave function (WAA), sum of the square root of square of the charge on all atom of the molecule (QA) and sum of the square root of square of the charge on all fluorine atoms in the molecule was obtained as the QSAR model in the present study with good statistical qualities (R 2 =0.937, R 2 adj=0.928, F=104.11, R 2 pred=0.929 and Q 2 =0.913). The QSAR model was used to study estimate the anti-MES activities of 1H-pyrazole-5-carboxylic acid derivatives not yet synthesized. 10 out of the 101 screened compounds had improved anti-MES activity when compared to the template (i.e. ethyl 4-(4-chlorophenyl)-3-morpholino-1H-pyrrole-2-carboxylate, which is compound number 61 in the dataset) used to design the 101 derivatives. These 10 compounds were docked with voltage-gated sodium channel (PDB code: 2KaV) and their binding affinity were comparable to that of phenytoin (a standard drug known to possess anti-MES activity).
Research in Pharmaceutical Biotechnology, Mar 31, 2014
Moringa oleifera Lam. (Moringaceae family) is a deciduous plant with tuber-like root at the earli... more Moringa oleifera Lam. (Moringaceae family) is a deciduous plant with tuber-like root at the earlier stage. Starch was isolated from the young tuber of the plant and examined instrumentally for its functional groups, X-ray diffractometer (XRD) profile, elemental analysis and antioxidant activities. The Fourier transform infrared spectroscopy analysis shows that peaks at 3465.23 to 3577.11 cm −1 represent OH stretch of alcohol; 3385.18 cm −1 represents O-H band of carboxylic acid; 3116.11 cm −1 represents =CH stretch of alkenes; 1647.26 cm −1 represents C=C stretch of alkenes and 1023.27 cm −1 represents CO stretch. The result of elemental analysis revealed that the starch granules contained: Fe (430.19 ppm), Cu (0.055 ppm) and Zn (0.19 ppm). XRD pattern revealed that the starch granules is an amorphous material and contained iron complex (C 24 H 16 FeN 10). The radical scavenging activity of the plant extract against DPPH (Sigma-Aldrich) was determined by UV-visible spectrophotometer at 517 nm. The result showed higher absorbance of the reaction mixture which indicated lower free radical scavenging activity and the degree of increment in absorbance measurement is indicative of the radical scavenging power of the extract, hence the anti-oxidant capacity and scavenging activity of the starch suspension revealed that it has a very low activity and percentage inhibition when compared with the ascorbic acid standard.
International Research Journal of Pure and Applied Chemistry, 2016
The multi-target quantitative structure-activity relationship (mt-QSAR) study of human immunodefi... more The multi-target quantitative structure-activity relationship (mt-QSAR) study of human immunodeficiency virus (HIV-1) inhibitors was addressed by applying a modest, hitherto active linear regression model based on the Genetic function approximation. QSAR studies were performed on two datasets of HIV-1 inhibitors targeted on integrase and reverse transcriptase, respectively. By using the genetic function approximation method, the collaboration among different set of inhibitors was exploited and an efficient multi-target QSAR modeling for HIV-1 inhibitors was obtained. The predictive quality of the mt-QSAR models was tested for an external set of 30 compounds, randomly chosen out of 150 compounds. The linear regression model based on the Genetic function approximation with eight selected descriptors was obtained. The accuracy of the Original Research Article
The Journal of Engineering and Exact Sciences, 2018
Quantitative structure-activity relationship study was done on some quinazoline-4(3H)-ones deriva... more Quantitative structure-activity relationship study was done on some quinazoline-4(3H)-ones derivatives with anticonvulsant activity against maximal electroshock-induced seizure. The quinazoline derivatives used as dataset and their anticonvulsant activity value were obtained from the literature. The molecular structure of the dataset compounds was generated with Spartan 14 software. This was optimized with PM3 semi-empirical quantum mechanical method available in the software. Molecular descriptors were obtained from the optimized structures using the PaDEL-Descriptor software. Activity values of the compounds and molecular descriptors obtained from the optimized structure made up the database for the study. The database was divided into training and test sets with Kennard Stone algorithm. Genetic function algorithm was used to develop quantitative structure-activity relationship models. The best model obtained was stable, robust and had good statistical parameters including determination coefficient R 2 (0.899), adjusted determination coefficient R 2 adj (0.888), variance ratio F (82.03), leave one out cross-validated determination coefficient Q 2 (0.866) and predicted determination coefficient for the test set R 2 pred (0.7406). The model indicated that the anticonvulsant activity of the studied compounds was dependent on Broto-Moreau autocorrelation-lag2/weighted by Vander Waals volume (ATS2v), average coefficient sum of the last eigenvector from Barysz matrix/weighted by Vander Waals volume (VE2_DZv), largest absolute eigenvalue of Burden matrix-6/weighted by relative atomic mass (SpMax6_Bhm), average valence path of order 6 and radial distribution function at 4.5 interatomic distance weighted by first ionization potential (RDF45i). k e y w o r d s Epilepsy Quantitative structure activity relationship Kennard-Stone algorithm Genetic function algorithm Quinazolinone ring system j c e c JCEC
Preparations of the complexes Preparation of the Cu[N-FMBH]SO 4 .2H 2 O complex 2g (0.0093 mol) o... more Preparations of the complexes Preparation of the Cu[N-FMBH]SO 4 .2H 2 O complex 2g (0.0093 mol) of N-FMBH was dissolved in 150 ml absolute ethanol and 2.33g (0.0093 mol) of CuSO 4 .5H 2 O was dissolved in 25 ml of distilled deionized water. The N-FMBH solution was then poured gently into the metal ion Abstract N'((furan-2-yl) methylene) benzohydrazide (N-FMBH) and 2-(2-aminothiazol-4-yl) acetohydrazide (2-ATCH) were prepared and characterized by melting point and infra-red studies. Their complexes with some M(II) sulphates (M = Mn, Co, Ni and Cu) were synthesized and characterized by melting point, solubility, infra-red and electronic spectral studies. The ligands are mainly neutral bidentate donors ligating via the carbonyl O and the primary amino N (or the azomethine N in the case of N-FMBH). The nickel, manganese and cobalt complexes are octahedral while the copper complexes are square planar respectively. The ligands and complexes showed some activity against Bacillus subtilis, Staphlyococus aureus, Escherichia coli and Klebseila pneumonia.
Quantitative structure-activity relationship study was done on 62 compounds with anticonvulsant a... more Quantitative structure-activity relationship study was done on 62 compounds with anticonvulsant activity in maximal electroshock-induced seizures test. The molecular structure of the compounds was optimized with parametric semi-empirical PM3 method available in Spartan 14 software. Quantum mechanical descriptors were extracted from the property and output module of the software. Combination of activity based-clustering and genetic function algorithm chemo-metric techniques were used to map molecular descriptors to activity values. A well-validated and robust quantitative structure-activity model was obtained with R2 = 0.947, Q2= 0.924, F = 91.42 and R2pred(test) = 0.881. The descriptor contained in the model suggested an increase in the number of O and N atoms in the molecule augments the activity of the studied compounds. Also, the introduction of electron donating substituents is beneficial to the activity of the studied compounds. Armed with these, information, new hypothetical1H...
The leaves of Loranthus micranthus Linn on shear butter tree was harvested in Suleja Nigeria for ... more The leaves of Loranthus micranthus Linn on shear butter tree was harvested in Suleja Nigeria for phytochemical screening, antioxidant activities, antimicrobial properties and proximate analyses. The crude ethanol extract of L. micranthus was observed for its antimicrobial activities at various concentrations (60, 30 and 15 µg/disc) using agar diffusion method, and was tested on Staphylococcus aureus, Escherichia coli, Salmonella paratyhi-1, Klebbsiella pneumoniae, and Proteus mirabilis and the results documented. Gradient extractions of ethanol (A), petroleum-spirit (B) and ethyl acetate (C) extracts were screened for phytochemical analysis and the result for ethanol extract showed positive results for tannins, glycosides, saponins, phenols, cardiac glycosides, phlobatanins, volatile oil, steroids and balsams; petroleum spirit extract indicated positive result for tannin, phenols, alkaloids, cardenolides, terpenoids, flavonoids, carbohydrates, resins, and volatile oil. While ethyl a...
Journal of Computational Methods in Molecular Design, 2015
Quantitative Structure Property Relationship (QSPR) analysis was applied to 36 Persistent Organic... more Quantitative Structure Property Relationship (QSPR) analysis was applied to 36 Persistent Organic Pollutants (POPs) using a combination of 0D, 1D, 2D and 3D molecular descriptors obtained by Semi empirical (pm3) method. The computed descriptors were correlated with the log of their experimental octanol-air partition coefficient (pKOA).Genetic function approximation was used to derive the most statistically significant QSPR model as a calibration model for predicting the pKOA of this class of molecules. Among the obtained QSPR models, the most statistically significant one was a five parameter linear equation with the squared correlation coefficient R2 value of 0.9889, adjusted squared correlation coefficient R2adj value of 0.9860 and Leave one out (LOO) cross validation coefficient (Q2) value of 0.9827. An external set was used for confirming the predictive power of the model (R2pred. = 0.7471). It is envisaged that the QSPR results identified in this study will offer an efficient a...
Journal of King Saud University - Science, 2018
Quantitative structure-activity relationship (QSAR) and molecular docking studies have been done ... more Quantitative structure-activity relationship (QSAR) and molecular docking studies have been done on 28 isoxazole and thiazole derivatives with anticonvulsant activity in subcutaneous pentylenetetrazole animal model. Physicochemical parameters obtained from PaDEL-Descriptors were utilized in the study. Parametric semi-empirical quantum technique PM3 available in Spartan 14 program was used to optimize the molecular structure of the dataset compounds. Genetic function algorithm, Modified-K-Medoid clustering, correlation analysis and multiple linear regressions were used to search for the best QSAR model. The model obtained had good statistical parameters (LOF = 0.056, R 2 = 0.975, Q 2 = 0.959, F 3,15 = 198.058, R 2 (Pred.) = 0.761, PRESS = 0.058, SEE = 0.062 and c R 2 P = 0.887) and can be utilized to predict the anticonvulsant activity of compounds that are within its chemical space. Molecular docking analysis showed that the studied compounds had a better binding affinity for c-aminobutyrate aminotransferase than vigabatrin which is a known inhibitor of c-aminobutyrate aminotransferase.
Journal of King Saud University - Science, 2018
Computational study was carried out to develop a Quantitative structure-activity relationship (QS... more Computational study was carried out to develop a Quantitative structure-activity relationship (QSAR) model and molecular docking studies on 4-Phenoxynicotinamide and 4-Phenoxypyrimidine-5-carboxamide derivatives as potent anti-diabetic agent. Chemical structure of these molecules were optimized with Density Functional Theory (DFT) utilizing the B3LYP with 6-31G* basis set. Five QSAR models were generated using Multi-Linear Regression and Genetic Function Approximation (GFA). Model one was selected as the optimum model and reported based on validation parameters which were found to be statistically significant with squared correlation coefficient (R 2) of 0.9460, adjusted squared correlation coefficient (R 2 adj) value of 0.9352 and cross validation coefficient () value of 0.9252. The chosen model was subjected to external validations and the model was found to have (R 2 test) of 0.8642. Molecular docking studies revealed that the binding affinities of the compounds correlate with their pEC 50 and the best compound has binding affinity of-10.4 kcal/mol which formed hydrogen bond and hydrophobic interaction and with amino acid residues of TGR5 receptor. QSAR model generated and molecular docking results propose the direction for the design of new anti-diabetic agent with better activity against TGR5 target site.
Journal of King Saud University - Science, 2018
DFT quantum mechanical method B3LYP/631G ⁄⁄ was used to optimize the molecular geometry of some 2... more DFT quantum mechanical method B3LYP/631G ⁄⁄ was used to optimize the molecular geometry of some 2-amino-N-benzylacetamide derivatives with anticonvulsant activities. Molecular descriptors were extracted from the optimized structure and used together with their activity as the database for the study. Kennard-Stone algorithm, genetic function algorithm, and multiple linear regressions were used to build a robust quantitative structure-activity relationship model. The quality of the model was shown by its parameters: R 2 (0.9270), R 2 adj (0.9178), F 8,63 (100.02), Q 2 (0.9036) and R 2 pred (0.7406). Therefore, the model can be used to predict the activity of new chemicals that within its applicability domain. The x-component of molecular dipole moment (d x), HOMO-LUMO energy gap (De), electrophilicity index (X), square of ovality (U 2), anisotropy of the polarizability (b 2), topological electronic index (T E), square root of the sum of square of charges on all hydrogen (QH) and square root of the sum of square of charges on all nitrogen (QN) are the descriptors that influenced the anticonvulsant activity of the studied compounds. This information can be utilized in the future to optimize the anticonvulsant activity of the studied compounds.
Beni-Suef University Journal of Basic and Applied Sciences, 2018
Chemometric descriptors were used to analyze quantitatively the anticonvulsant activity of ninety... more Chemometric descriptors were used to analyze quantitatively the anticonvulsant activity of ninety propanamide derivatives. Molecular geometries of the data set were optimized with B3LYP/6-31G * * quantum mechanical method and chemometric descriptors were calculated from the optimized structure. Linear QSAR models were developed using genetic function algorithm. Predictive capabilities of the models were evaluated using various internal and external validation techniques. The best three models proposed were octa-parametric equation with good statistical quality: R 2 (0.898-0.918); Q 2 (0.865-0.893); R 2 pred (0.746-0.772) and F (66.657-88.036). 2acetamido-N-benzyl-2-(5-methylfuran-2-yl) acetamide a member of the data set was chosen as scaffold for in silico design. Using the information afforded by the models, several attempts were made to optimize the scaffold by introducing various modifications. Potential derivatives with higher predicted activity values than the template were identified and a detailed analysis on the models applicability domain defined the designed compounds, whose estimations can be accepted with confidence. Some of the designed compounds docked with γ-aminobutyrate aminotransferase (PBD: 1OHV) (target) showed better binding affinity for the target when compare with 4-aminohex-5-enoic acid (vigabatrin) (a known inhibitor of the target).
The Journal of Engineering and Exact Sciences, 2018
Quantitative structure activity relationship study (QSAR) and molecular docking were used to desi... more Quantitative structure activity relationship study (QSAR) and molecular docking were used to design and virtually screen some new N-benzylacetamide derivatives for their ability to inhibit ?-amino butyrate-aminotransferase. Ninety compounds with anticonvulsant activity against maximal electroshock induced seizures were used for QSAR study. B3LYP/6-31G** quantum mechanical method was employed to optimize/minimize the molecular structure of these compounds. Genetic Function Algorithm (GFA) method was used to develop the QSAR models. Each model gave an octa-parametric equation with good statistical qualities (R2 ranged from 0.823 to 0.893, Q2 from 0.772 to 0.854, F from 36.53 to 37.10, R2pred(test) from 0.768 to 0.893). Information obtained from the parameter contained in the model suggested that increasing the molecular mass and linearity of molecule would lead to increase in anticonvulsant activity of studied compounds. These informed the design and virtual screening of 118 new N-ben...
Beni-Suef University Journal of Basic and Applied Sciences, 2018
Computational methods were used to study the structural parameters that influence that anticonvul... more Computational methods were used to study the structural parameters that influence that anticonvulsant activity of some α-aminoacetamides which were active in maximal electroshock seizure test. Their molecular structures were optimized with B3LYP/631G** density function theory method using Spartan 14 software. Modified-Kmediod clustering algorithm was used for data division, genetic function algorithm was used for variable selection and multiple linear regressions method was used for model construction. Developed model was statistically significant with coefficient of determination (R 2) of 0.957, cross-validated R 2 i.e. Q 2 of 0.927, variance ratio (F 4,15) of 82.94, Y-randomization R 2 i.e. c R 2 P of 0.840 and predicted R 2 (R 2 Pred) of 0.812. The molecular descriptors contained in the model were GATS8c (Geary autocorrelation of lag-8/weighted by atomic charges); VCH-7 (valence chain of order 7); VE3_D (Logarithmic coefficient sum of the last eigenvector from topological distance matrix) and RDF100p (radial distribution function − 100/weighted by polarizability). Molecular docking result showed that studied compounds had high binding affinity for neuronal sodium channel (PDB: 2KaV). Their binding affinity compared favorably with that of phenytoin, a validated sodium channel blocker. In addition, a linear relationship existed between anticonvulsant activity of studied compounds and their binding affinity for neuronal sodium channel.
Journal of the Turkish Chemical Society, Section A: Chemistry, 2017
A quantitative structure-activity relationship (QSAR) study was performed to develop a model that... more A quantitative structure-activity relationship (QSAR) study was performed to develop a model that relates the structures of 62 compounds, which have activity against maximal electroshock-induced seizure (MES), with their anti-MES activity. Molecular structures of the compounds were geometrically optimized and energetically minimized using a combination of modified Merck force field (MMFF) molecular mechanics, Austin model 1 (AM1) semi-empirical quantum mechanical and density functional theory (DFT) quantum mechanical method using the Becke's three parameter exchange functional (B3) hybrid with Lee, Yang and Parr correlation functional (LYP) and basis set of the double zeta split valence plus polarization quality 6-31G** i.e. B3LYP/6-31G**. Theoretically derived descriptors were obtained from the optimized structures, a genetic function approximation (GFA) algorithm was also applied to select the optimal descriptors and multiple linear regression (MLR) was used to establish a relationship between the anti-MES activity of the compounds and the optimal molecular descriptors. A six-parametric equation containing dipole moment (μ), energy of the lowest unoccupied molecular orbital (ϵLUMO), polar surface area (PSA), accessible surface area derived from wave function (WAA), sum of the square root of square of the charge on all atom of the molecule (QA) and sum of the square root of square of the charge on all fluorine atoms in the molecule was obtained as the QSAR model in the present study with good statistical qualities (R 2 =0.937, R 2 adj=0.928, F=104.11, R 2 pred=0.929 and Q 2 =0.913). The QSAR model was used to study estimate the anti-MES activities of 1H-pyrazole-5-carboxylic acid derivatives not yet synthesized. 10 out of the 101 screened compounds had improved anti-MES activity when compared to the template (i.e. ethyl 4-(4-chlorophenyl)-3-morpholino-1H-pyrrole-2-carboxylate, which is compound number 61 in the dataset) used to design the 101 derivatives. These 10 compounds were docked with voltage-gated sodium channel (PDB code: 2KaV) and their binding affinity were comparable to that of phenytoin (a standard drug known to possess anti-MES activity).
Research in Pharmaceutical Biotechnology, Mar 31, 2014
Moringa oleifera Lam. (Moringaceae family) is a deciduous plant with tuber-like root at the earli... more Moringa oleifera Lam. (Moringaceae family) is a deciduous plant with tuber-like root at the earlier stage. Starch was isolated from the young tuber of the plant and examined instrumentally for its functional groups, X-ray diffractometer (XRD) profile, elemental analysis and antioxidant activities. The Fourier transform infrared spectroscopy analysis shows that peaks at 3465.23 to 3577.11 cm −1 represent OH stretch of alcohol; 3385.18 cm −1 represents O-H band of carboxylic acid; 3116.11 cm −1 represents =CH stretch of alkenes; 1647.26 cm −1 represents C=C stretch of alkenes and 1023.27 cm −1 represents CO stretch. The result of elemental analysis revealed that the starch granules contained: Fe (430.19 ppm), Cu (0.055 ppm) and Zn (0.19 ppm). XRD pattern revealed that the starch granules is an amorphous material and contained iron complex (C 24 H 16 FeN 10). The radical scavenging activity of the plant extract against DPPH (Sigma-Aldrich) was determined by UV-visible spectrophotometer at 517 nm. The result showed higher absorbance of the reaction mixture which indicated lower free radical scavenging activity and the degree of increment in absorbance measurement is indicative of the radical scavenging power of the extract, hence the anti-oxidant capacity and scavenging activity of the starch suspension revealed that it has a very low activity and percentage inhibition when compared with the ascorbic acid standard.
International Research Journal of Pure and Applied Chemistry, 2016
The multi-target quantitative structure-activity relationship (mt-QSAR) study of human immunodefi... more The multi-target quantitative structure-activity relationship (mt-QSAR) study of human immunodeficiency virus (HIV-1) inhibitors was addressed by applying a modest, hitherto active linear regression model based on the Genetic function approximation. QSAR studies were performed on two datasets of HIV-1 inhibitors targeted on integrase and reverse transcriptase, respectively. By using the genetic function approximation method, the collaboration among different set of inhibitors was exploited and an efficient multi-target QSAR modeling for HIV-1 inhibitors was obtained. The predictive quality of the mt-QSAR models was tested for an external set of 30 compounds, randomly chosen out of 150 compounds. The linear regression model based on the Genetic function approximation with eight selected descriptors was obtained. The accuracy of the Original Research Article
The Journal of Engineering and Exact Sciences, 2018
Quantitative structure-activity relationship study was done on some quinazoline-4(3H)-ones deriva... more Quantitative structure-activity relationship study was done on some quinazoline-4(3H)-ones derivatives with anticonvulsant activity against maximal electroshock-induced seizure. The quinazoline derivatives used as dataset and their anticonvulsant activity value were obtained from the literature. The molecular structure of the dataset compounds was generated with Spartan 14 software. This was optimized with PM3 semi-empirical quantum mechanical method available in the software. Molecular descriptors were obtained from the optimized structures using the PaDEL-Descriptor software. Activity values of the compounds and molecular descriptors obtained from the optimized structure made up the database for the study. The database was divided into training and test sets with Kennard Stone algorithm. Genetic function algorithm was used to develop quantitative structure-activity relationship models. The best model obtained was stable, robust and had good statistical parameters including determination coefficient R 2 (0.899), adjusted determination coefficient R 2 adj (0.888), variance ratio F (82.03), leave one out cross-validated determination coefficient Q 2 (0.866) and predicted determination coefficient for the test set R 2 pred (0.7406). The model indicated that the anticonvulsant activity of the studied compounds was dependent on Broto-Moreau autocorrelation-lag2/weighted by Vander Waals volume (ATS2v), average coefficient sum of the last eigenvector from Barysz matrix/weighted by Vander Waals volume (VE2_DZv), largest absolute eigenvalue of Burden matrix-6/weighted by relative atomic mass (SpMax6_Bhm), average valence path of order 6 and radial distribution function at 4.5 interatomic distance weighted by first ionization potential (RDF45i). k e y w o r d s Epilepsy Quantitative structure activity relationship Kennard-Stone algorithm Genetic function algorithm Quinazolinone ring system j c e c JCEC