Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation
Today, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2022/5031577 |
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| author | Farnaz Salehi Leila Emami Zahra Rezaei Soghra Khabnadideh Behnaz Tajik Razieh Sabet |
| author_facet | Farnaz Salehi Leila Emami Zahra Rezaei Soghra Khabnadideh Behnaz Tajik Razieh Sabet |
| author_sort | Farnaz Salehi |
| collection | DOAJ |
| description | Today, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient compounds with higher resistance are needed. In this study, a series of a fluconazole analogues were subjected to quantitative structure-activity relationship analysis to find the structure requirements for modeling adequate candidate. The best multiple linear regression equation was achieved from GA-PLS and MLR modeling. Subsequently, in silico screening study was applied to found new potent lead compounds based on the resulted model. The ability of the best designed compounds for antifungal activity was investigated by using molecular dynamic (MD) and molecular docking simulation. The results showed that compound F13 can efficiently bind to lanestrol 14-α demethylase target similar to other antifungal azoles. The molecular docking studies revealed an interesting binding profile with very high receptor affinity to the CYP51 active site. The triazole moiety of ligand F13 pointed to HEM group in lanestrol 14-α demethylase site and coordinated to Fe of HEM through its N4 atom. Also, there was a convenient relevance between QSAR and docking results. With the compound F13 which demonstrated the most promising minimum inhibitory concentration (MIC) values, it can be concluded that F13 is appropriate candidate for the development as antifungal agent. |
| format | Article |
| id | doaj-art-9ad76cf11bb44662aa993a0bc9eac4a8 |
| institution | Kabale University |
| issn | 2090-9071 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-9ad76cf11bb44662aa993a0bc9eac4a82025-02-03T05:58:56ZengWileyJournal of Chemistry2090-90712022-01-01202210.1155/2022/5031577Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics SimulationFarnaz Salehi0Leila Emami1Zahra Rezaei2Soghra Khabnadideh3Behnaz Tajik4Razieh Sabet5Faculty of Pharmacy and Pharmaceutical Sciences Research CenterDepartment of Medicinal ChemistryDepartment of Medicinal ChemistryFaculty of Pharmacy and Pharmaceutical Sciences Research CenterDepartment of Medicinal ChemistryDepartment of Medicinal ChemistryToday, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient compounds with higher resistance are needed. In this study, a series of a fluconazole analogues were subjected to quantitative structure-activity relationship analysis to find the structure requirements for modeling adequate candidate. The best multiple linear regression equation was achieved from GA-PLS and MLR modeling. Subsequently, in silico screening study was applied to found new potent lead compounds based on the resulted model. The ability of the best designed compounds for antifungal activity was investigated by using molecular dynamic (MD) and molecular docking simulation. The results showed that compound F13 can efficiently bind to lanestrol 14-α demethylase target similar to other antifungal azoles. The molecular docking studies revealed an interesting binding profile with very high receptor affinity to the CYP51 active site. The triazole moiety of ligand F13 pointed to HEM group in lanestrol 14-α demethylase site and coordinated to Fe of HEM through its N4 atom. Also, there was a convenient relevance between QSAR and docking results. With the compound F13 which demonstrated the most promising minimum inhibitory concentration (MIC) values, it can be concluded that F13 is appropriate candidate for the development as antifungal agent.http://dx.doi.org/10.1155/2022/5031577 |
| spellingShingle | Farnaz Salehi Leila Emami Zahra Rezaei Soghra Khabnadideh Behnaz Tajik Razieh Sabet Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation Journal of Chemistry |
| title | Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation |
| title_full | Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation |
| title_fullStr | Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation |
| title_full_unstemmed | Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation |
| title_short | Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation |
| title_sort | fluconazole like compounds as potential antifungal agents qsar molecular docking and molecular dynamics simulation |
| url | http://dx.doi.org/10.1155/2022/5031577 |
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