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Hinokiflavone and Related C-O-C-Type Biflavonoids as Anti-cancer Compounds: Properties and Mechanism of Action
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Jean-François Goossens, Laurence Goossens, Christian Bailly
Natural Products and Bioprospecting. 2021, 11 (4): 365-377.
DOI: 10.1007/s13659-021-00298-w
Biflavonoids are divided in two classes: C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone (HNK) with an ether linkage between the two connected apigenin units. This later sub-group of bisflavonyl ethers includes HNK, ochnaflavone, delicaflavone and a few other dimeric compounds, found in a variety of plants, notably Selaginella species. A comprehensive review of the anticancer properties and mechanism of action of HNK is provided, to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives, and HNK-containing plant extracts. The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9 (with a potential direct binding to MMP-9). In addition, HNK was found to function as a potent modulator of pre-mRNA splicing, inhibiting the SUMO-specific protease SENP1. As such, HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds. Oral formulations of HNK have been elaborated to enhance its solubility, to facilitate the compound delivery and to enhance its anticancer efficacy. The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK. This compound deserves further attention as a regulator of pre-mRNA splicing, useful to treat cancers (in particular hepatocellular carcinoma) and other human pathologies.
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α-C(sp3)-H Arylation of Cyclic Carbonyl Compounds
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Mei Wang, Wei Wang, Dashan Li, Wen-Jing Wang, Rui Zhan, Li-Dong Shao
Natural Products and Bioprospecting. 2021, 11 (4): 379-404.
DOI: 10.1007/s13659-021-00312-1
α-C(sp3)-H arylation is an important type of C-H functionalization. Various biologically significant natural products, chemical intermediates, and drugs have been effectively prepared via C-H functionalization. Cyclic carbonyl compounds comprise of cyclic ketones, enones, lactones, and lactams. The α-C(sp3)-H arylation of these compounds have been exhibited high efficiency in forming C(sp3)-C(sp2) bonds, played a crucial role in organic synthesis, and attracted majority of interests from organic and medicinal communities. This review focused on the most significant advances including methods, mechanism, and applications in total synthesis of natural products in the field of α-C(sp3)-H arylations of cyclic carbonyl compounds in recent years.
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Diterpenoid Alkaloids from the Aerial Parts of Aconitum flavum Hand. -Mazz
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Na Zhang, Fan Xia, Song-Yu Li, Yin Nian, Li-Xin Wei, Gang Xu
Natural Products and Bioprospecting. 2021, 11 (4): 421-429.
DOI: 10.1007/s13659-021-00302-3
Sixteen diterpenoid alkaloids (DAs), including six aconitine-type alkaloids (5 and 9-13), seven 7,17-seco-aconitine-type alkaloids (1-4, 6-8), two napelline-type alkaloids (14 and 15) as well as one veatchine-type alkaloid (16), were isolated from the aerial parts of Aconitum fl avum Hand.-Mazz. In which, flavumolines A-D (1-4) were four new ones, and flavumoline E (5) was reported as natural compound for the first time. Their chemical structures were elucidated by the analysis of extensive spectroscopic data. The inhibitory activities of these isolates on Cav3.1 low voltage-gated Ca2+ channel, NO production in LPS-activated RAW264.7cells, five human tumor cell lines, as well as acetylcholinesterase (AChE) were tested.
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Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast
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Richard Alexander Lewis, Jenileima Devi, Katherine Green, Juanjuan Li, Adam Hopkins, Jacqueline Hayles, Paul Nurse, Jeff Errington, Nicholas Edward Ellis Allenby
Natural Products and Bioprospecting. 2021, 11 (4): 431-445.
DOI: 10.1007/s13659-021-00304-1
This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a “rounded” or “small” cellular morphological phenotype. Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain, SAK950 showed that many induced a “rounded” phenotype. We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes. We show that five of the strains produced streptothricin and that 26 strains produced polyenes, including fungichromin, filipin and candicidin, the last of which was produced by 24 strains. A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S. albidofl avus whilst those that additionally produced streptothricin were related to S. enissocaesilis. A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern. The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S. pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.
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New Secodaphnane-Type Alkaloids with Cytotoxic Activities from Daphniphyllum angustifolium Hutch
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Qing-Yun Lu, Jia-Hui Zhang, Ying-Yao Li, Xue-Xue Pu, Cui-Shan Zhang, Shuai Liu, Jia-Jia Wan, Ying-Tong Di, Xiao-Jiang Hao
Natural Products and Bioprospecting. 2021, 11 (4): 453-457.
DOI: 10.1007/s13659-021-00309-w
One new Daphniphyllum alkaloid, daphnioldhanol A (1), together with three known ones, were isolated from the stem part of Daphniphyllum angustifolium Hutch. Their structures were elucidated by spectroscopic methods and comparing with the literature data. Compound 2 is a new natural product, but known by synthesis as a racemate. Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9 μM.
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Tangutidines A-C, Three Amphoteric Diterpene Alkaloids from Aconitum tanguticum
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Hao-Yi Li, Bing-Chao Yan, Li-Xin Wei, Han-Dong Sun, Pema-Tenzin Puno
Natural Products and Bioprospecting. 2021, 11 (4): 459-464.
DOI: 10.1007/s13659-021-00310-3
Three new diterpene alkaloids, tangutidines A-C (1-3), and four known alkaloids (4-7) were isolated from the whole plant of Aconitum tanguticum, from which amphoteric diterpene alkaloids (1-3) were obtained for the first time. The structures of 1-3 were elucidated by detailed interpretation of spectroscopic data, including MS and NMR data. All of them were evaluated for their cytotoxic activities.
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