Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.76891
Sadia Sultan, G. K. S. Singh, K. Ashraf, M. Ashraf
Docking is a powerful approach to perform virtual screening on large library of compounds, rank the conformations using a scoring function, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. Using experimentally proven active compounds, detailed docking studies were performed to determine the mech-anism of molecular interaction and its binding mode in the active site of the modeled yeast α -glucosidase and human intestinal maltase-glucoamylase. All active ligands were found to have greater binding affinity with the yeast α -glucosidase as compared to that of human homologs, intestinal, and pancreatic maltase, by an average value of ~ (cid:1) 1.3 and ~ (cid:1) 0.8 kcal/ mol, respectively. Thirty quinoline derivatives have been synthesized and evaluated against β -glucuronidase inhibitory potential. Twenty-four analogs, which showed outstanding β glucuronidase activity, have IC 50 values ranging between 2.11 (cid:3) 0.05 and 46.14 (cid:3) 0.95 μ M than standard D-saccharic acid 1,4-lactone (IC 50 = 48.4 (cid:3) 1.25 μ M). Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. In addition, Small series of morpholine hydrazones synthesized to form morpholine hydrazones scaffold. The in vitro anti-cancer potential of all these compounds were checked against human cancer cell lines such as HepG2 (Human hepatocellular liver carcinoma) and MCF-7 (Human breast adenocarcinoma). Molecular docking studies were also performed to understand the binding interaction.
{"title":"Molecular Docking Studies of Enzyme Inhibitors and Cytotoxic Chemical Entities","authors":"Sadia Sultan, G. K. S. Singh, K. Ashraf, M. Ashraf","doi":"10.5772/INTECHOPEN.76891","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76891","url":null,"abstract":"Docking is a powerful approach to perform virtual screening on large library of compounds, rank the conformations using a scoring function, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. Using experimentally proven active compounds, detailed docking studies were performed to determine the mech-anism of molecular interaction and its binding mode in the active site of the modeled yeast α -glucosidase and human intestinal maltase-glucoamylase. All active ligands were found to have greater binding affinity with the yeast α -glucosidase as compared to that of human homologs, intestinal, and pancreatic maltase, by an average value of ~ (cid:1) 1.3 and ~ (cid:1) 0.8 kcal/ mol, respectively. Thirty quinoline derivatives have been synthesized and evaluated against β -glucuronidase inhibitory potential. Twenty-four analogs, which showed outstanding β glucuronidase activity, have IC 50 values ranging between 2.11 (cid:3) 0.05 and 46.14 (cid:3) 0.95 μ M than standard D-saccharic acid 1,4-lactone (IC 50 = 48.4 (cid:3) 1.25 μ M). Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. In addition, Small series of morpholine hydrazones synthesized to form morpholine hydrazones scaffold. The in vitro anti-cancer potential of all these compounds were checked against human cancer cell lines such as HepG2 (Human hepatocellular liver carcinoma) and MCF-7 (Human breast adenocarcinoma). Molecular docking studies were also performed to understand the binding interaction.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"303 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74541909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.75720
Dr. Ravi Varala, B. Babu
Introduction to tetrazole and click chemistry approaches was briefed in a concise way in order to help the readers have a basic understanding. Tetrazole and its derivatives play very important role in medicinal and pharmaceutical applications. The synthesis of tetrazole derivatives can be approached in ecofriendly approaches such as the use of water as solvent, moderate conditions, nontoxic, easy extractions, easy setup, low cost, etc. with good to excellent yields.
{"title":"A Click Chemistry Approach to Tetrazoles: Recent Advances","authors":"Dr. Ravi Varala, B. Babu","doi":"10.5772/INTECHOPEN.75720","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75720","url":null,"abstract":"Introduction to tetrazole and click chemistry approaches was briefed in a concise way in order to help the readers have a basic understanding. Tetrazole and its derivatives play very important role in medicinal and pharmaceutical applications. The synthesis of tetrazole derivatives can be approached in ecofriendly approaches such as the use of water as solvent, moderate conditions, nontoxic, easy extractions, easy setup, low cost, etc. with good to excellent yields.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90537062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.73920
Rafael Trindade Maia and Vinícius Costa Amador
In this chapter, we pointed some relevant results obtained by protein-ligand docking simulations in the context of insecticide and herbicide resistance performed by glutathione S-transferases (GSTs), a detoxifying superfamily enzyme. We present here some in silico evidences of GST binding against chemical insecticides in the malaria and dengue vectors ( Anopheles gambiae and Aedes aegypti mosquitoes) and against chemical herbicides used on rice ( Oryza sativa ) culture. Our findings suggest that some members from epsilon class (GSTE2, GSTE5) can metabolize some insecticide compounds and that a tau class member (GSTU4) can metabolize some herbicides. The results reinforce the importance of docking studies for enzyme activity comprehension. These information can allow in the future the implementation of new strategies for mosquito control and herbicide man-agement on rice culture through biotechnological improvements designed to specific GST targets. Induced mutations on catalytic binding sites of GSTU4 could improve rice herbicide resistance and minimize produce damage, while rational compounds can be designed to inhibit GSTE members to decline insecticide resistance on mosquito control. In both cases, biotechnological tools could be developed focusing on GSTs that would reduce environmental impact by the use of insecticide and herbicide.
{"title":"Molecular Docking for Detoxifying Enzyme Studies","authors":"Rafael Trindade Maia and Vinícius Costa Amador","doi":"10.5772/INTECHOPEN.73920","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.73920","url":null,"abstract":"In this chapter, we pointed some relevant results obtained by protein-ligand docking simulations in the context of insecticide and herbicide resistance performed by glutathione S-transferases (GSTs), a detoxifying superfamily enzyme. We present here some in silico evidences of GST binding against chemical insecticides in the malaria and dengue vectors ( Anopheles gambiae and Aedes aegypti mosquitoes) and against chemical herbicides used on rice ( Oryza sativa ) culture. Our findings suggest that some members from epsilon class (GSTE2, GSTE5) can metabolize some insecticide compounds and that a tau class member (GSTU4) can metabolize some herbicides. The results reinforce the importance of docking studies for enzyme activity comprehension. These information can allow in the future the implementation of new strategies for mosquito control and herbicide man-agement on rice culture through biotechnological improvements designed to specific GST targets. Induced mutations on catalytic binding sites of GSTU4 could improve rice herbicide resistance and minimize produce damage, while rational compounds can be designed to inhibit GSTE members to decline insecticide resistance on mosquito control. In both cases, biotechnological tools could be developed focusing on GSTs that would reduce environmental impact by the use of insecticide and herbicide.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"327 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76351913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.72995
Pintilie Lucia, A. Stefaniu
Molecular docking studies have been carried out for a better understanding of the drug- receptor interactions. All the synthesized compounds have been subjected to molecular docking against targets that have been chosen based on the specific mechanism of action of the quinolones used in the antibacterial activity screening. A study of the characteristics and molecular properties of the small molecule known as ligand has been realized. In the first stage of the study, the 2D and 3D structures have been generated. The most stable conformer for each structure was obtained by geometry optimization and energy minimization. A series of topological, conformational characteristics and QSAR properties, important to assess the flexibility and the ability of the studied conformer to bind to the protein receptor, were deter- mined and analyzed. These properties were discussed in order to assess the flexibility and the binding ability of studied conformers to bind to the receptor protein. The docking stud - ies have been carried out. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolones in the active site of the protein receptor. morpholine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the HOMO of 7-pyrrolidinyl-8-unsubstituted-quinolone, FPQ 35 electron density is localized on pyrrolidine heterocyclic, on aromatic ring and on 4-oxo group. For the HOMO of 7-pyrro-lidinyl-8-chloro-quinolone, FPQ 36 electron density is localized on pyrrolidine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the LUMO of 7-substituted-8-unsubstituted-quinolones, NF, PF, FPQ27, O 83, FPQ 24, FPQ 32, electron density of FPQ 25 and FPQ 35 is localized on 4-piridinona ring and on aromatic ring. For the LUMO of 7-substituted-8-chloro-quinolones, electron density of FPQ 50, FPQ 51, FPQ29, O 85, FPQ 30, FPQ 33, FPQ 28 and FPQ 36 is localized on 4-piridinona ring, on aromatic ring B and on chlorine atom. For the 6-cloroqinolones, the electron density is located in the same manner as the corresponding fluoroquinolones.
{"title":"Docking Studies on Novel Analogues of 8-Chloro-Quinolones against Staphylococcus aureus","authors":"Pintilie Lucia, A. Stefaniu","doi":"10.5772/INTECHOPEN.72995","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72995","url":null,"abstract":"Molecular docking studies have been carried out for a better understanding of the drug- receptor interactions. All the synthesized compounds have been subjected to molecular docking against targets that have been chosen based on the specific mechanism of action of the quinolones used in the antibacterial activity screening. A study of the characteristics and molecular properties of the small molecule known as ligand has been realized. In the first stage of the study, the 2D and 3D structures have been generated. The most stable conformer for each structure was obtained by geometry optimization and energy minimization. A series of topological, conformational characteristics and QSAR properties, important to assess the flexibility and the ability of the studied conformer to bind to the protein receptor, were deter- mined and analyzed. These properties were discussed in order to assess the flexibility and the binding ability of studied conformers to bind to the receptor protein. The docking stud - ies have been carried out. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolones in the active site of the protein receptor. morpholine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the HOMO of 7-pyrrolidinyl-8-unsubstituted-quinolone, FPQ 35 electron density is localized on pyrrolidine heterocyclic, on aromatic ring and on 4-oxo group. For the HOMO of 7-pyrro-lidinyl-8-chloro-quinolone, FPQ 36 electron density is localized on pyrrolidine heterocyclic, on aromatic ring, on 4-oxo group and on chlorine atom. For the LUMO of 7-substituted-8-unsubstituted-quinolones, NF, PF, FPQ27, O 83, FPQ 24, FPQ 32, electron density of FPQ 25 and FPQ 35 is localized on 4-piridinona ring and on aromatic ring. For the LUMO of 7-substituted-8-chloro-quinolones, electron density of FPQ 50, FPQ 51, FPQ29, O 85, FPQ 30, FPQ 33, FPQ 28 and FPQ 36 is localized on 4-piridinona ring, on aromatic ring B and on chlorine atom. For the 6-cloroqinolones, the electron density is located in the same manner as the corresponding fluoroquinolones.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87855573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.72994
Abel Suárez-Castro, M. Valle-Sánchez, C. Cortés-García, L. Chacón-García
Molecular modeling applies several computational chemistry tools as molecular docking; this latter has been useful in medicinal chemistry for prediction of interactions between small ligands and biological targets measuring angles, enthalpy and other physicalchemical properties involved in the supramolecular entities. In this chapter, we present molecular docking advances with a perspective to the improvement of parameterization including halogen bonding interactions (XB) and the modification of scoring functions based on halogen sigma-hole polarization. At the same time, we have included the current computational methods to study halogen bonding that increased the accuracy of predicted entities. Finally, we present examples of the main force fields including electronic distribution and modifications for halogen atoms.
{"title":"Molecular Docking in Halogen Bonding","authors":"Abel Suárez-Castro, M. Valle-Sánchez, C. Cortés-García, L. Chacón-García","doi":"10.5772/INTECHOPEN.72994","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72994","url":null,"abstract":"Molecular modeling applies several computational chemistry tools as molecular docking; this latter has been useful in medicinal chemistry for prediction of interactions between small ligands and biological targets measuring angles, enthalpy and other physicalchemical properties involved in the supramolecular entities. In this chapter, we present molecular docking advances with a perspective to the improvement of parameterization including halogen bonding interactions (XB) and the modification of scoring functions based on halogen sigma-hole polarization. At the same time, we have included the current computational methods to study halogen bonding that increased the accuracy of predicted entities. Finally, we present examples of the main force fields including electronic distribution and modifications for halogen atoms.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87648484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.72895
L. Landeros-Martínez, D. Glossman-Mitnik, E. Orrantia-Borunda, N. Flores-Holguín
Additional information available the chapter Abstract The molecular docking of tamoxifen ’ s metabolites, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxy-N-desmethyl-tamoxifen, in estrogen and progesterone hor- mone receptors was studied in aqueous solution. The metabolites 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxy-N-desmethyl-tamoxifen exhibit a binding energy in the estrogen receptor cavity of (cid:1) 10.69 kcal/mol, (cid:1) 10.9 kcal/mol, and (cid:1) 11.35 kcal/mol, respectively, and (cid:1) 1.45 kcal/mol, (cid:1) 9.29 kcal/mol, and (cid:1) 0.38 kcal/mol in the progesterone receptor. This indicates a spontaneous interaction between the metabolites and the active sites in the hormone receptors. Docking has an adequate accuracy for both receptors, and from this calculation the active site residues were defined for the different metabolites and the estrogen and progesterone receptors. Also, the chemical reactivity of the amino acids of the active sites of each metabolite was determined. These reactivity properties were obtained within the framework of density functional theory, using the functional M06 with the basis set 6-31G (d). The results indicate that in the estrogen receptor, the highest charge transfer of the three analyzed metabolites is in the union of the metabolite and the Leu346-Thr347 residue. The progesterone receptor shows minor tendency to react with higher hardness values than the estrogen receptor. The hydrogen bonds are three for the estrogen receptor in two different metabolites, while in progesterone only one is formed with the N-desmethyl-tamoxifen metabolite.
{"title":"A Combined Molecular Docking and Electronic Structure Study for a Breast Cancer Drug Design","authors":"L. Landeros-Martínez, D. Glossman-Mitnik, E. Orrantia-Borunda, N. Flores-Holguín","doi":"10.5772/INTECHOPEN.72895","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72895","url":null,"abstract":"Additional information available the chapter Abstract The molecular docking of tamoxifen ’ s metabolites, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxy-N-desmethyl-tamoxifen, in estrogen and progesterone hor- mone receptors was studied in aqueous solution. The metabolites 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxy-N-desmethyl-tamoxifen exhibit a binding energy in the estrogen receptor cavity of (cid:1) 10.69 kcal/mol, (cid:1) 10.9 kcal/mol, and (cid:1) 11.35 kcal/mol, respectively, and (cid:1) 1.45 kcal/mol, (cid:1) 9.29 kcal/mol, and (cid:1) 0.38 kcal/mol in the progesterone receptor. This indicates a spontaneous interaction between the metabolites and the active sites in the hormone receptors. Docking has an adequate accuracy for both receptors, and from this calculation the active site residues were defined for the different metabolites and the estrogen and progesterone receptors. Also, the chemical reactivity of the amino acids of the active sites of each metabolite was determined. These reactivity properties were obtained within the framework of density functional theory, using the functional M06 with the basis set 6-31G (d). The results indicate that in the estrogen receptor, the highest charge transfer of the three analyzed metabolites is in the union of the metabolite and the Leu346-Thr347 residue. The progesterone receptor shows minor tendency to react with higher hardness values than the estrogen receptor. The hydrogen bonds are three for the estrogen receptor in two different metabolites, while in progesterone only one is formed with the N-desmethyl-tamoxifen metabolite.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85185488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-07-11DOI: 10.5772/INTECHOPEN.72898
Mark. A. Phillips, Marisa A. Stewart, Darby L. Woodling, Zhong-Ru Xie
Molecular docking has been developed and improving for many years, but its ability to bring a medicine to the drug market effectively is still generally questioned. In this chapter, we introduce several successful cases including drugs for treatment of HIV, cancers, and other prevalent diseases. The technical details such as docking software, protein data bank (PDB) structures, and other computational methods employed are also collected and displayed. In most of the cases, the structures of drugs or drug candidates and the interacting residues on the target proteins are also presented. In addition, a few successful examples of drug repurposing using molecular docking are mentioned in this chapter. It should provide us with confidence that the docking will be extensively employed in the industry and basic research. Moreover, we should actively apply molecular docking and related technology to create new therapies for diseases.
{"title":"Has Molecular Docking Ever Brought us a Medicine?","authors":"Mark. A. Phillips, Marisa A. Stewart, Darby L. Woodling, Zhong-Ru Xie","doi":"10.5772/INTECHOPEN.72898","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72898","url":null,"abstract":"Molecular docking has been developed and improving for many years, but its ability to bring a medicine to the drug market effectively is still generally questioned. In this chapter, we introduce several successful cases including drugs for treatment of HIV, cancers, and other prevalent diseases. The technical details such as docking software, protein data bank (PDB) structures, and other computational methods employed are also collected and displayed. In most of the cases, the structures of drugs or drug candidates and the interacting residues on the target proteins are also presented. In addition, a few successful examples of drug repurposing using molecular docking are mentioned in this chapter. It should provide us with confidence that the docking will be extensively employed in the industry and basic research. Moreover, we should actively apply molecular docking and related technology to create new therapies for diseases.","PeriodicalId":19002,"journal":{"name":"Molecular Docking","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75495129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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