Insight of Natural Compounds Halimane Diterpenoids against Mycobacterium tuberculosis: Virtual Screening, DFT, Drug-Likeness, and Molecular Dynamics Approach  

作　　者：Laurent Gael Eyia Andiga Boris Davy Bekono Désiré Mama Bikele Pie Pascal Onguéné Amoa Luc Calvin Owono Owono Luc Léonard Mbaze Meva’a Laurent Gael Eyia Andiga;Boris Davy Bekono;Désiré Mama Bikele;Pie Pascal Onguéné Amoa;Luc Calvin Owono Owono;Luc Léonard Mbaze Meva’a(Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon;Department of Physics, Ecole Normale Suprieure, University of Yaound 1, Yaound, Cameroon;Center for Drug Discovery, Faculty of Science, University of Buea, Buea, Cameroon;Department of Chemistry, University of Yaound I Institute of Wood Technology, Mbalmayo, Cameroon;CEPAMOQ, Faculty of Science, University of Douala, Douala, Cameroon)

机构地区：[1]Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon [2]Department of Physics, Ecole Normale Suprieure, University of Yaound 1, Yaound, Cameroon [3]Center for Drug Discovery, Faculty of Science, University of Buea, Buea, Cameroon [4]Department of Chemistry, University of Yaound I Institute of Wood Technology, Mbalmayo, Cameroon [5]CEPAMOQ, Faculty of Science, University of Douala, Douala, Cameroon

出　　处：《Computational Molecular Bioscience》2024年第2期35-58,共24页计算分子生物学（英文）

摘　　要：In the purpose to design novel antituberculosis (anti-TB) drugs agents against Mycobacterium tuberculosis (Mtb), we have built a molecular library around 42 Halimane Diterpenoids isolated from natural sources. Two Mtb enzymes drug targets (Mtb Mycothiol S-transferase and Mtb Homoserine transacetylase) have been adopted. The pharmacological potential was investigated through molecular docking, molecular dynamics simulation, density functional theory (gas phase and water) and ADMET analysis. Our results indicate that (2R,5R,6S)-1,2,3,4,5,6,7,8-octahydro-5-((E)-5-hydroxy-3-methylpent-3-enyl)-1,1,5,6-tetramethylnaphtha-lene-2-ol (compound 20) has displays higher docking score with each of the selected drug targets. In addition, this molecule exhibits a satisfactory drug potential activity and a good chemical reactivity. Its improved kinetic stability in the Mtb Mycothiol S-transferase enzyme reflects its suitability as a novel inhibitor of Mtb growth. This molecule has displayed a good absorption potential. Our results also show that its passive passage of the intestinal permeability barrier is more effective than that of first-line treatments (ethambutol, isoniazid). In the same way, this anti-TB druglikeness has shown to be able to cross the blood brain barrier.In the purpose to design novel antituberculosis (anti-TB) drugs agents against Mycobacterium tuberculosis (Mtb), we have built a molecular library around 42 Halimane Diterpenoids isolated from natural sources. Two Mtb enzymes drug targets (Mtb Mycothiol S-transferase and Mtb Homoserine transacetylase) have been adopted. The pharmacological potential was investigated through molecular docking, molecular dynamics simulation, density functional theory (gas phase and water) and ADMET analysis. Our results indicate that (2R,5R,6S)-1,2,3,4,5,6,7,8-octahydro-5-((E)-5-hydroxy-3-methylpent-3-enyl)-1,1,5,6-tetramethylnaphtha-lene-2-ol (compound 20) has displays higher docking score with each of the selected drug targets. In addition, this molecule exhibits a satisfactory drug potential activity and a good chemical reactivity. Its improved kinetic stability in the Mtb Mycothiol S-transferase enzyme reflects its suitability as a novel inhibitor of Mtb growth. This molecule has displayed a good absorption potential. Our results also show that its passive passage of the intestinal permeability barrier is more effective than that of first-line treatments (ethambutol, isoniazid). In the same way, this anti-TB druglikeness has shown to be able to cross the blood brain barrier.

关 键 词：Antituberculosis Druglikeness Density Functional Theory Halimane Diterpenoids Molecular Docking Molecular Dynamics Simulation 

分 类 号：O62[理学—有机化学]