The essential oil of Lonicera nummulariifolia Jaub & Spach was analyzed by GC and GC/MS. Eighty-t... more The essential oil of Lonicera nummulariifolia Jaub & Spach was analyzed by GC and GC/MS. Eighty-three components were identified in the oil. Spathulenol (21.6%), α-muurolol (14.1%), β-caryophyllene (6.8%), α-cadinol (5.4%) and bicyclogermacrene (5.1%) were the main compounds in the oil.
The human immunodeficiency viruses type 1 reverse transcriptase is a major target for drug develo... more The human immunodeficiency viruses type 1 reverse transcriptase is a major target for drug development. Inhibition of this enzyme has been one of the primary therapeutic strategies in suppressing the replication of human immunodeficiency viruses type 1. A series of 2-amino-6-arylsulfonylbenzonitrile derivatives was subjected to quantitative structure–activity relationship analysis. The newly proposed substituent electronic descriptors were investigated for quantitative structure–activity relationship modeling of the compounds and a comparison was made with the conventional molecular descriptors. Two chemometrics methods including multiple linear regressions and partial least squares combined with genetic algorithm for variable selection were employed to make connections between structural parameters and enzyme inhibition. The results revealed the significant roles of topological, geometrical and substituent electronic descriptor parameters on the human immunodeficiency viruses type 1 reverse transcriptase inhibitory activity of the studied molecules. The selected substituent electronic descriptor parameters revealed that more electronegative and less polar substituents as meta position and more electrophile substituents as para positions are favorable for higher activity. It was found that electronic descriptors calculated for substituents (substituent electronic descriptor parameters) could explain 80% of variances in the biological activity data. The most significant quantitative structure–activity relationship model, obtained by partial least squares combined with genetic algorithm, could explain and predict 90% and 85% of variances in the pIC50 data, respectively.
A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones, namely 2-alkyl-3-hydroxy-5-N-pipe... more A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones, namely 2-alkyl-3-hydroxy-5-N-piperidylmethyl or N,N-dialkylaminomethyl pyridine-4-ones 9, 10 and 15-18, two derivatives of N-aryl-2methyl-3-hydroxy-pyridine-4-ones 19, 20 and two N-alkyl derivatives of maltol, 21 and 22 were prepared. They were screened for their antibacterial and antifungal activities against a variety of microorganisms using micro plate Alamar Blue Ò assay (MABA) method. Multiple linear regressions (MLR) analysis was performed for the synthesized compounds as well as a series of pyridinone and pyranone derivatives 23-43 which have been synthesized and evaluated for antimicrobial activity by other researchers previously. Studied compounds showed a better quantitative structure-activity relationship (QSAR) model for the antimicrobial activity against Candida albicans and Staphylococcus aureus in comparison with other tested microorganisms.
Six Schiff base derivatives of D-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-D-man... more Six Schiff base derivatives of D-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-D-mannitol (6: aryl = XC 6 H 4 : X = o-, m-and p-Cl or NO 2 ), have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H 37 Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in lg/mL. All three nitro derivatives exhibit significant activities: activities of (6d: X = o-NO 2 ), (6e: X = m-NO 2 ) and (6f: X = p-NO 2 ) are 12.5, 25.0 and 25.0 lg/mL, respectively. When compared with first line drugs, such as ethambutol, they can be considered as a good starting point to develop new lead compounds for the treatment of multidrug-resistant tuberculosis. Characterization of the new compounds 6 is generally achieved spectroscopically. The structure of compound 3 has been confirmed by X-ray crystallography.
Quantitative structure activity relationships (QSAR) of anti-cancer isatin derivatives were disco... more Quantitative structure activity relationships (QSAR) of anti-cancer isatin derivatives were discovered by multiple linear regressions (MLR) and genetic algorithm partial least squares (GA-PLS) methods. Topological, chemical, geometrical and functional groups descriptors were found to be effective parameters on the cytotoxic activity. The positive effects of the number of halogen atoms and the number of total secondary carbons, and the negative effects of the number of secondary amides, and the number of ketones on the anti-cancer activity were in agreement with previous SAR studies. Hansch analysis showed the importance of lipophilic R(3) and R(5) substituents. Between MLR and GA-PLS, MLR represented superior results with a high statistical quality (R(2)=0.92 and Q(2)=0.90) for predicting the activity of the compounds.
Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory... more Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid sulfonamide derivatives were discovered. We have demonstrated the detailed application of two efficient nonlinear methods for evaluation of quantitative structureeactivity relationships of the studied compounds. Components produced by principal component analysis as input of developed nonlinear models were used. The performance of the developed models namely PC-GRNN and PC-LS-SVM were tested by several validation methods. The resulted PC-LS-SVM model had a high statistical quality (R 2 ¼ 0:91 and R 2 CV ¼ 0:81) for predicting the cytotoxic activity of the compounds. Comparison between predictability of PC-GRNN and PC-LS-SVM indicates that later method has higher ability to predict the activity of the studied molecules.
A series of 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives were subjected to quanti... more A series of 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives were subjected to quantitative structure-antimicrobial activity relationships (QSAR) analysis. A collection of chemometrics methods, including factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR) and partial least squares combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and antimicrobial activity. The results revealed the significant role of topological parameters in the antimicrobial activity of the studied compounds against S. aureus and C. albicans. The most significant QSAR model, obtained by GA-PLS, could explain and predict 96% and 91% of variances in the pIC(50) data (compounds tested against S. aureus) and predict 91% and 87% of variances in the pIC(50) data (compounds tested against C. albicans), respectively.
Abstract Quantitative relationships between molecular structure and methionine aminopeptidase-2 i... more Abstract Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid sulfonamides were determined by the partial least-squares (PLS) method. Evaluation of a test set of ten compounds with the developed PLS model revealed it is reliable and has good predictive power. Because the QSAR study was performed on the basis of theoretical descriptors calculated completely from molecular structure, the proposed model could potentially provide useful information about the activity of the compounds studied. Various tests and criteria, for example leave-one-out cross validation, leave-many-out cross validation, and criteria suggested by Tropsha, were used to examine the predictive power and robustness of the model. The model could explain and predict 73 and 64% of variances in the pIC 50 data. Graphical Abstract
The essential oil of Lonicera nummulariifolia Jaub & Spach was analyzed by GC and GC/MS. Eighty-t... more The essential oil of Lonicera nummulariifolia Jaub & Spach was analyzed by GC and GC/MS. Eighty-three components were identified in the oil. Spathulenol (21.6%), α-muurolol (14.1%), β-caryophyllene (6.8%), α-cadinol (5.4%) and bicyclogermacrene (5.1%) were the main compounds in the oil.
The human immunodeficiency viruses type 1 reverse transcriptase is a major target for drug develo... more The human immunodeficiency viruses type 1 reverse transcriptase is a major target for drug development. Inhibition of this enzyme has been one of the primary therapeutic strategies in suppressing the replication of human immunodeficiency viruses type 1. A series of 2-amino-6-arylsulfonylbenzonitrile derivatives was subjected to quantitative structure–activity relationship analysis. The newly proposed substituent electronic descriptors were investigated for quantitative structure–activity relationship modeling of the compounds and a comparison was made with the conventional molecular descriptors. Two chemometrics methods including multiple linear regressions and partial least squares combined with genetic algorithm for variable selection were employed to make connections between structural parameters and enzyme inhibition. The results revealed the significant roles of topological, geometrical and substituent electronic descriptor parameters on the human immunodeficiency viruses type 1 reverse transcriptase inhibitory activity of the studied molecules. The selected substituent electronic descriptor parameters revealed that more electronegative and less polar substituents as meta position and more electrophile substituents as para positions are favorable for higher activity. It was found that electronic descriptors calculated for substituents (substituent electronic descriptor parameters) could explain 80% of variances in the biological activity data. The most significant quantitative structure–activity relationship model, obtained by partial least squares combined with genetic algorithm, could explain and predict 90% and 85% of variances in the pIC50 data, respectively.
A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones, namely 2-alkyl-3-hydroxy-5-N-pipe... more A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones, namely 2-alkyl-3-hydroxy-5-N-piperidylmethyl or N,N-dialkylaminomethyl pyridine-4-ones 9, 10 and 15-18, two derivatives of N-aryl-2methyl-3-hydroxy-pyridine-4-ones 19, 20 and two N-alkyl derivatives of maltol, 21 and 22 were prepared. They were screened for their antibacterial and antifungal activities against a variety of microorganisms using micro plate Alamar Blue Ò assay (MABA) method. Multiple linear regressions (MLR) analysis was performed for the synthesized compounds as well as a series of pyridinone and pyranone derivatives 23-43 which have been synthesized and evaluated for antimicrobial activity by other researchers previously. Studied compounds showed a better quantitative structure-activity relationship (QSAR) model for the antimicrobial activity against Candida albicans and Staphylococcus aureus in comparison with other tested microorganisms.
Six Schiff base derivatives of D-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-D-man... more Six Schiff base derivatives of D-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-D-mannitol (6: aryl = XC 6 H 4 : X = o-, m-and p-Cl or NO 2 ), have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H 37 Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in lg/mL. All three nitro derivatives exhibit significant activities: activities of (6d: X = o-NO 2 ), (6e: X = m-NO 2 ) and (6f: X = p-NO 2 ) are 12.5, 25.0 and 25.0 lg/mL, respectively. When compared with first line drugs, such as ethambutol, they can be considered as a good starting point to develop new lead compounds for the treatment of multidrug-resistant tuberculosis. Characterization of the new compounds 6 is generally achieved spectroscopically. The structure of compound 3 has been confirmed by X-ray crystallography.
Quantitative structure activity relationships (QSAR) of anti-cancer isatin derivatives were disco... more Quantitative structure activity relationships (QSAR) of anti-cancer isatin derivatives were discovered by multiple linear regressions (MLR) and genetic algorithm partial least squares (GA-PLS) methods. Topological, chemical, geometrical and functional groups descriptors were found to be effective parameters on the cytotoxic activity. The positive effects of the number of halogen atoms and the number of total secondary carbons, and the negative effects of the number of secondary amides, and the number of ketones on the anti-cancer activity were in agreement with previous SAR studies. Hansch analysis showed the importance of lipophilic R(3) and R(5) substituents. Between MLR and GA-PLS, MLR represented superior results with a high statistical quality (R(2)=0.92 and Q(2)=0.90) for predicting the activity of the compounds.
Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory... more Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid sulfonamide derivatives were discovered. We have demonstrated the detailed application of two efficient nonlinear methods for evaluation of quantitative structureeactivity relationships of the studied compounds. Components produced by principal component analysis as input of developed nonlinear models were used. The performance of the developed models namely PC-GRNN and PC-LS-SVM were tested by several validation methods. The resulted PC-LS-SVM model had a high statistical quality (R 2 ¼ 0:91 and R 2 CV ¼ 0:81) for predicting the cytotoxic activity of the compounds. Comparison between predictability of PC-GRNN and PC-LS-SVM indicates that later method has higher ability to predict the activity of the studied molecules.
A series of 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives were subjected to quanti... more A series of 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives were subjected to quantitative structure-antimicrobial activity relationships (QSAR) analysis. A collection of chemometrics methods, including factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR) and partial least squares combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and antimicrobial activity. The results revealed the significant role of topological parameters in the antimicrobial activity of the studied compounds against S. aureus and C. albicans. The most significant QSAR model, obtained by GA-PLS, could explain and predict 96% and 91% of variances in the pIC(50) data (compounds tested against S. aureus) and predict 91% and 87% of variances in the pIC(50) data (compounds tested against C. albicans), respectively.
Abstract Quantitative relationships between molecular structure and methionine aminopeptidase-2 i... more Abstract Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid sulfonamides were determined by the partial least-squares (PLS) method. Evaluation of a test set of ten compounds with the developed PLS model revealed it is reliable and has good predictive power. Because the QSAR study was performed on the basis of theoretical descriptors calculated completely from molecular structure, the proposed model could potentially provide useful information about the activity of the compounds studied. Various tests and criteria, for example leave-one-out cross validation, leave-many-out cross validation, and criteria suggested by Tropsha, were used to examine the predictive power and robustness of the model. The model could explain and predict 73 and 64% of variances in the pIC 50 data. Graphical Abstract
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