Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in ...Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in the Drug Standard of the Ministry of Health of China.Twelve novel tryptamine-derived alkaloids(1−12)and eight known compounds(13−20)were isolated from P.harmala seeds.Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers,comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′linkage and C-3−C-4′connection,respectively.Compounds 3−5 were identified as indole-quinazoline heteromers,exhibiting a novel C-3 and NH-1′linkage between indole and quinazoline-derived fragments.Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer.Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton,featuring an unusual spiro-tricyclic ring(7)and conventional bicyclic tryptamine.Compounds 9−11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine.Compounds 1−3 and 6−11 were identified as racemates.Compounds 2,7,9,10,and 12 were confirmed via X-ray crystallographic analysis.All isolated compounds(1−20)exhibited varying degrees of antiviral efficacy against respiratory syncytial virus(RSV).Notably,the anti-RSV activity of compound 12(IC505.01±0.14μmol·L^(−1))surpassed that of the positive control(ribavirin,IC506.23±0.95μmol·L^(−1)),as validated through plaque reduction and immunofluorescence assays.The identification of anti-RSV compounds from P.harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.展开更多
Tryptamine-derived natural products have been discovered from different sources including animals, plants and bacteria,and they show various biological activities. However, they are not discovered widely compared with...Tryptamine-derived natural products have been discovered from different sources including animals, plants and bacteria,and they show various biological activities. However, they are not discovered widely compared with the large amounts of tryptamine derivatives generated by chemical synthesis. We here report the discovery of five tryptamine-derived natural products(1-5) and one known polyketide 6 from Bacillus sp. PKU-TA00001. Compounds 1 and 2 are new compounds featuring methyl-hexanamide moieties, compound 4 is first discovered as a natural product, and 3 and 4’s NMR data are first provided. All compounds showed MIC(minimum inhibitory concentration) values higher than 50 μM against several Gram-positive and negative strains, and showed no cytotoxicity at the concentration of 100 μM against the human cancer cell lines A549, HCT-8 and MCF-7. The discovery of 1-4 expands the structural diversity of tryptamine-derived natural products, and sets the stage for revealing their biosynthetic mechanisms and biological activities in the future.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82104015,82003609,and 81973190)the Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515110415,2020A1515110453,and 2020B1515020033)+1 种基金the Characteristic Innovation Project of General Universities in Guangdong Province(No.2024KTSCX167)the Science and Technology Planning Project of Guangzhou City(No.202201010485).
文摘Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in the Drug Standard of the Ministry of Health of China.Twelve novel tryptamine-derived alkaloids(1−12)and eight known compounds(13−20)were isolated from P.harmala seeds.Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers,comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′linkage and C-3−C-4′connection,respectively.Compounds 3−5 were identified as indole-quinazoline heteromers,exhibiting a novel C-3 and NH-1′linkage between indole and quinazoline-derived fragments.Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer.Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton,featuring an unusual spiro-tricyclic ring(7)and conventional bicyclic tryptamine.Compounds 9−11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine.Compounds 1−3 and 6−11 were identified as racemates.Compounds 2,7,9,10,and 12 were confirmed via X-ray crystallographic analysis.All isolated compounds(1−20)exhibited varying degrees of antiviral efficacy against respiratory syncytial virus(RSV).Notably,the anti-RSV activity of compound 12(IC505.01±0.14μmol·L^(−1))surpassed that of the positive control(ribavirin,IC506.23±0.95μmol·L^(−1)),as validated through plaque reduction and immunofluorescence assays.The identification of anti-RSV compounds from P.harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
基金National Natural Science Foundation of China(Grant No.81673332,81573326,81741148)
文摘Tryptamine-derived natural products have been discovered from different sources including animals, plants and bacteria,and they show various biological activities. However, they are not discovered widely compared with the large amounts of tryptamine derivatives generated by chemical synthesis. We here report the discovery of five tryptamine-derived natural products(1-5) and one known polyketide 6 from Bacillus sp. PKU-TA00001. Compounds 1 and 2 are new compounds featuring methyl-hexanamide moieties, compound 4 is first discovered as a natural product, and 3 and 4’s NMR data are first provided. All compounds showed MIC(minimum inhibitory concentration) values higher than 50 μM against several Gram-positive and negative strains, and showed no cytotoxicity at the concentration of 100 μM against the human cancer cell lines A549, HCT-8 and MCF-7. The discovery of 1-4 expands the structural diversity of tryptamine-derived natural products, and sets the stage for revealing their biosynthetic mechanisms and biological activities in the future.
