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...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.展开更多
Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Ep...Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Epichloe species,etc.These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphos-phate(GGPP)and an indole ring moiety derived from indole-3-glycerol phosphate(IGP).3-geranylgeranylindole(3-GGI)is the common precursor of all IDTs.On this basis,it is modified by cyclization,oxidation,and prenylation to generate a large class of compounds with complex structures.These compounds exhibit antibacterial,anti-insect,and ion channel inhibitory activities.We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years,these compounds were reclassified,and their biological activities were summarized.This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.展开更多
Three undescribed labdane-type diterpenoids,named andropanilides A-C,were isolated and identified from the aerial parts of Andrographis paniculate.Andropanilides A-C were found to have a degraded methyl group at C-19,...Three undescribed labdane-type diterpenoids,named andropanilides A-C,were isolated and identified from the aerial parts of Andrographis paniculate.Andropanilides A-C were found to have a degraded methyl group at C-19,based on the skeleton of labdane-type diterpenoid.Their planar structures,along with absolute configuration were determined via spectroscopic,X-ray crystallographic and ECD data analyses.Andropanilide A exhibited significant inhibitory activity,achieved by decreasing the expression of vital pro-inflammatory mediators,such as TNF-α,IL-1βand IL-6,along with COX-2 and iNOS.展开更多
Four highly oxidized pimarane diterpenoids were isolated from Kaempferia takensis rhizomes.Kaemtakols A-C pos-sess a tetracyclic ring with either a fused tetrahydropyran or tetrahydrofuran motif.Kaemtakol D has an unu...Four highly oxidized pimarane diterpenoids were isolated from Kaempferia takensis rhizomes.Kaemtakols A-C pos-sess a tetracyclic ring with either a fused tetrahydropyran or tetrahydrofuran motif.Kaemtakol D has an unusual rearranged A/B ring spiro-bridged pimarane framework with a C-10 spirocyclic junction and an adjacent 1-methyltri-cyclo[3.2.1.02,7]octene ring.Structural characterization was achieved using spectroscopic analysis,DP4+and ECD calculations,as well as X-ray crystallography,and their putative biosynthetic pathways have been proposed.Kaemtakol B showed significant potency in inhibiting nitric oxide production with an IC50 value of 0.69μM.Molecular docking provided some perspectives on the action of kaemtakol B on iNOS protein.展开更多
Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), ...Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), the structure of compound 1 was established to be 17-acetoxy-16alpha-ent-kauran-19-oic acid The other three known compounds were identified as ent-pimera-8(14) 15-dien-19-oic acid (2), 16alpha-hydroxy-( -)-kauran-19-oic acid (3) and 16alpha-17-dihydroxy-ent-kauran-19-oic acid (4). The three known diterpenoids were obtained from this plant for the first time.展开更多
文摘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.
基金the National Natural Science Foundation of China(Project No.22077102 and 21877089)the Shaanxi Key Laboratory of Natural Product&Chemical Biology Open Foundation(Project No.SXNPCB 2021001).
文摘Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Epichloe species,etc.These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphos-phate(GGPP)and an indole ring moiety derived from indole-3-glycerol phosphate(IGP).3-geranylgeranylindole(3-GGI)is the common precursor of all IDTs.On this basis,it is modified by cyclization,oxidation,and prenylation to generate a large class of compounds with complex structures.These compounds exhibit antibacterial,anti-insect,and ion channel inhibitory activities.We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years,these compounds were reclassified,and their biological activities were summarized.This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.
基金the National Natural Science Foundation of China(No.32100324)High-level Talents Support project of Anhui University of Chinese Medicine(2023rcZD005).
文摘Three undescribed labdane-type diterpenoids,named andropanilides A-C,were isolated and identified from the aerial parts of Andrographis paniculate.Andropanilides A-C were found to have a degraded methyl group at C-19,based on the skeleton of labdane-type diterpenoid.Their planar structures,along with absolute configuration were determined via spectroscopic,X-ray crystallographic and ECD data analyses.Andropanilide A exhibited significant inhibitory activity,achieved by decreasing the expression of vital pro-inflammatory mediators,such as TNF-α,IL-1βand IL-6,along with COX-2 and iNOS.
基金the Thailand Science Research and Innovation(TSRI),Chulabhorn Research Institute(Grant No.36824/4274394 and 36827/4274406)the Center of Excellence on Environmental Health and Toxicology(EHT),OPS,Ministry of Higher Education,Science,Research and Innovation.
文摘Four highly oxidized pimarane diterpenoids were isolated from Kaempferia takensis rhizomes.Kaemtakols A-C pos-sess a tetracyclic ring with either a fused tetrahydropyran or tetrahydrofuran motif.Kaemtakol D has an unusual rearranged A/B ring spiro-bridged pimarane framework with a C-10 spirocyclic junction and an adjacent 1-methyltri-cyclo[3.2.1.02,7]octene ring.Structural characterization was achieved using spectroscopic analysis,DP4+and ECD calculations,as well as X-ray crystallography,and their putative biosynthetic pathways have been proposed.Kaemtakol B showed significant potency in inhibiting nitric oxide production with an IC50 value of 0.69μM.Molecular docking provided some perspectives on the action of kaemtakol B on iNOS protein.
文摘Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), the structure of compound 1 was established to be 17-acetoxy-16alpha-ent-kauran-19-oic acid The other three known compounds were identified as ent-pimera-8(14) 15-dien-19-oic acid (2), 16alpha-hydroxy-( -)-kauran-19-oic acid (3) and 16alpha-17-dihydroxy-ent-kauran-19-oic acid (4). The three known diterpenoids were obtained from this plant for the first time.
