Four unreported aporphine alkaloids with antifungal activities from Artabotrys hexapetalus.

In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5-10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.

Chromosome level genome assembly of endangered medicinal plant Anisodus tanguticus.

Anisodus tanguticus is a medicinal herb that belongs to the Anisodus genus of the Solanaceae family. This endangered herb is mainly distributed in Qinghai-Tibet Plateau. In this study, we combined the Illumina short-read, Nanopore long-read and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to de novo assemble the A. tanguticus genome. A high-quality chromosomal-level genome assembly was obtained with a genome size of 1.26 Gb and a contig N50 of 25.07 Mb. Of the draft genome sequences, 97.47% were anchored to 24 pseudochromosomes with a scaffold N50 of 51.28 Mb. In addition, 842.14 Mb of transposable elements occupying 66.70% of the genome assembly were identified and 44,252 protein-coding genes were predicted. The genome assembly of A. tanguticus will provide genetic repertoire to understand the adaptation strategy of Anisodus species in the plateau, which will further promote the conservation of endangered A. tanguticus resources.

Phytochemical Analysis of Nothapodytes tomentosa and Distribution and Content of Camptothecin and its Analogues in Four Plants.

Camptothecin (CPT) and its derivatives have attracted worldwide attention because of their notable anticancer activity. However, the growing demand for CPT in the global pharmaceutical industry has caused a severe shortage of CPT-producing plant resources. In this study, phytochemical analysis of Nothapodytes tomentosa results in the isolation and identification of CPT (13: ) and 16 analogues (1:  - 12, 14:  - 17: ), including a new (1: ) and five known (9, 10, 12, 15: , and 17: ) CPT analogues with an open E-ring. In view of the potential anticancer activity of CPT analogues with an open E-ring, the fragmentation pathways and mass spectra profiles of these six CPT analogues (1, 9, 10, 12, 15: , and 17: ) are investigated, providing a reference for the rapid detection of these compounds in other plants. Furthermore, based on the fragmentation patterns of CPT (13: ) and known analogues (2:  - 8, 11, 14, 16, 18:  - 26: ), the distribution and content of these compounds in different tissues of N. tomentosa, N. nimmoniana, Camptotheca acuminata, and Ophiorrhiza japonica are further studied. Our findings not only provide an alternative plant resource for further expanding the development and utilization of CPT and its analogues, but also lay a foundation for improving the utilization of known CPT-producing plant resources.

Advances in chemistry and bioactivity of the genus Erythroxylum.

Erythroxylum P. Browne is the largest and most representative genus of Erythroxylaceae family. It contains approximately 230 species that are mainly distributed in tropical and subtropical regions. Some species in this genus, such as E. monogynum and E. coca, have been used as folk medicines in India or South America for a long history. It is well known that Erythroxylum plants are rich in tropane alkaloids, and the representative member cocaine shows remarkable activity in human central nervous system. However, many other types of active compounds have also been found in Erythroxylum along with the broadening and deepening of phytochemical research. To date, a total of 383 compounds from Erythroxylum have been reported, among which only 186 tropane alkaloids have been reviewed in 2010. In this review, we summarized all remained 197 compounds characterized from 53 Erythroxylum species from 1960 to 2021, which include diterpenes, triterpenes, alkaloids, flavonoids, and other derivates, providing a comprehensive overview of phytoconstituents profile of Erythroxylum plants. In addition, the biological activities of representative phytochemicals and crude extracts were also highlighted.

Characterization of inthomycin biosynthetic gene cluster revealing new insights into carboxamide formation.

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B (1) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the 15N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.

Functional genomics analysis reveals two novel genes required for littorine biosynthesis.

Some medicinal plants of the Solanaceae produce pharmaceutical tropane alkaloids (TAs), such as hyoscyamine and scopolamine. Littorine is a key biosynthetic intermediate in the hyoscyamine and scopolamine biosynthetic pathways. However, the mechanism underlying littorine formation from the precursors phenyllactate and tropine is not completely understood. Here, we report the elucidation of littorine biosynthesis through a functional genomics approach and functional identification of two novel biosynthesis genes that encode phenyllactate UDP-glycosyltransferase (UGT1) and littorine synthase (LS). UGT1 and LS are highly and specifically expressed in Atropa belladonna secondary roots. Suppression of either UGT1 or LS disrupted the biosynthesis of littorine and its TA derivatives (hyoscyamine and scopolamine). Purified His-tagged UGT1 catalysed phenyllactate glycosylation to form phenyllactylglucose. UGT1 and LS co-expression in tobacco leaves led to littorine synthesis if tropine and phenyllactate were added. This identification of UGT1 and LS provides the missing link in littorine biosynthesis. The results pave the way for producing hyoscyamine and scopolamine for medical use by metabolic engineering or synthetic biology.

Cangumycins A-F, six new angucyclinone analogues with immunosuppressive activity from Streptomyces.

Cangumycins A-F (1-6), six new angucyclinone analogues, together with two known ones (7 and 8), were isolated from the fermentation broth of a soil-derived Streptomyces sp. KIB-M10. Structures of these compounds were elucidated via a joint use of spectroscopic analyses and single-crystal X-ray diffractions. Among them, cangumycins E (5) and F (6) share a C-ring cleaved backbone, and cangumycins B (2) and E (5) exhibit potent immunosuppressive activity (IC50 8.1 and 2.7 µmol·L-1, respectively) against human T cell proliferation at a non-cytotoxic concentration.

A new actinomycin Z analogue with an additional oxygen bridge between chromophore and ß-depsipentapeptide from Streptomyces sp. KIB-H714.

Actinomycin Z6 (1), a new member of the actinomycin family, along with three congeners of the Z-type (Z1, Z3, Z5) actinomycins, are produced from Streptomyces sp. KIB-H714. Their structures were authenticated by comprehensive spectroscopic data interpretation. Different from all the reported Z-type actinomycins, the ß-ring of the new compound actinomycin Z6 includes an additional ring linked between the actinoyl chromophore and ß-peptidolactone. In Z3 and Z5, the L-threonine in ß-depsipeptide is replaced by the unusual 4-chlorothreonine, an amino acid rarely found in actinomycin family. All isolates were evaluated for cytotoxicity against five human tumor cell lines and for inhibitory activity against Candida albicans and Staphylococcus aureus.

New phloroglucinol derivatives with protein tyrosine phosphatase 1B (PTP1B) inhibitory activities from Syzygium austroyunnanense.

Five new phloroglucinol derivatives (1-5) together with one known analogue (6) were isolated from the leaves of Syzygium austroyunnanense which is an edible folk medicine used for the treatment of diabetes. The new structures were elucidated as austroyunones A - E (1-5) by means of the extensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR). Compounds 4-6 showed obvious protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. This discovery of new phloroglucinols and their bioactivities provided a scientific basis for the application of S. austroyunnanense as an edible and medicinal plant.

Cytotoxicity-Guided Isolation of Two New Phenolic Derivatives from Dryopteris fragrans (L.) Schott.

Dryopteris fragrans is a valuable medicinal plant resource with extensive biological activities including anti-cancer, anti-oxidation, and anti-inflammation activities. This work aims to study further the cytotoxic constituents from Dryopteris fragrans. In this work, two new phenolic derivatives known as dryofragone (1) and dryofracoumarin B (2) with six known compounds (3⁻8) were isolated from the petroleum ether fraction of the methanol extract of the aerial parts of Dryopteris fragrans (L.) Schott by two round cytotoxicity-guided tracking with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell counting kit-8 (CCK-8) assay. Their structures were elucidated by the extensive spectroscopic analysis (¹H-NMR, 13C-NMR, and two dimensions NMR), chemical derivatization, and comparison with data reported in the literature. All the isolates were evaluated for their cytotoxicity against nine cancer cell lines as well as their in vitro immunomodulatory activity. The results showed that compounds have a modest cytotoxicity toward human HeLa cell line with IC50 value below 30 µM and compounds 4 and 5 may modulate immunity to affect the growth of tumor cells.

Bioactive acylphloroglucinols with adamantyl skeleton from Hypericum sampsonii.

Hyperisampsins A-D (1-4), with tetracyclo[6.3.1.1(3,10).0(3,7)]tridecane skeletons and seven biogenetically related congeners (5-11), were isolated from Hypericum sampsonii. Their structures were elucidated by comprehensive spectroscopic techniques. The absolute configuration of 1 was established by ECD calculations, and those of 5 and 9 were confirmed by single X-ray crystallographic analyses. Hyperisampsins A and D showed potent anti-HIV activities with EC50 of 2.97 and 0.97 µM and selectivity index of 4.80 and 7.70, respectively.

19-oxygenated ent-kaurane diterpenoids from Isodon pharicus.

Eight new 19-oxygenated ENT-kaurane diterpenoids were isolated from the aerial parts of Isodon pharicus. Their structures were determined by means of extensive spectroscopic techniques including interpretation of 1D and 2D NMR spectra. Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3, MCF-7, and SH-SY5Y cell lines.

Three new arylnaphthalene lignans from Schisandra propinqua var. sinensis.

Three new arylnaphthalene lignans, named sinensisins A-C (1-3), together with three known compounds, were isolated from the aerial parts of Schisandra propinqua var. sinensis. Their structures were established by spectroscopic methods, and compound 1 exhibited weak anti-HIV-1 activity with an TI value of 6.7.

Schisanartane nortriterpenoids with diverse post-modifications from Schisandra propinqua.

Twenty-one highly oxygenated nortriterpenoids with a schisanartane skeleton were isolated from the stems of Schisandra propinqua var. propinqua. These nortriterpenoids featured a polycyclic framework composed of 7/8/5 consecutive carbocycles, which were organized by similar 5/5/7/5/7/5 rings A-F and varied oxygen-containing rings G and H. A biosynthetic classification of these compounds is proposed on the basis of their diverse post-modifications.

Bisnortriterpenoids possessing an 18-Nor-schiartane skeleton from Schisandra propinqua var. propinqua.

Six C (28) triterpenoids with an 18-nor-schiartane framework were isolated from the aerial parts of SCHISANDRA PROPINQUA var. PROPINQUA. The new compounds, propindilactones P-S ( 1- 4), were structurally characterized by extensive spectroscopic methods. New compounds 2 and 3, together with known wuweizidilactones B and H ( 5- 6), were evaluated for their anti-HBV activity.

Screening of polycyclic polyprenylated acylphloroglucinols from Garcinia species using precursor ion discovery (PID) scan and ultra performance liquid chromatography electrospray ionization Q-TOF tandem mass spectrometry.

A strategy was newly developed to rapidly screen polycyclic polyprenylated acyl-phloroglucinols (PPAPs) from the plant matrices of nine Garcinia species using ultra-performance liquid chromatography (UPLC) coupled with comprehensive mass spectrometric approaches including precursor ion discovery (PID) and tandem mass (MS/MS) scans. The PPAPs share the same diagnostic product ion at m/z 177.02 in positive MS/MS scan, which may be increased as the base peak by ramping the cone voltage from 45 to 100 V. With this ramping cone voltage PID scan, it is feasible to selectively screen the PPAPs from 29 samples of nine Garcinia species. This approach has proven to be a powerful, highly selective, and sensitive tool for rapid screening and detection of nontargeted components in natural products before the purification and structural elucidation process.

ent-Kaurane diterpenoids from Isodon pharicus.

Phytochemical investigation of the aerial parts of Isodon pharicus led to the isolation of 13 new ent-kaurane diterpenoids, compounds 1-13, together with 12 known analogues (14-25). The structures of the new compounds were determined by means of extensive spectroscopic techniques including interpretation of 1D and 2D NMR spectra. Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3, MCF-7, and SH-SY5Y cell lines.

Bioassay-guided isolation of xanthones and polycyclic prenylated acylphloroglucinols from Garcinia oblongifolia.

Bioassay-guided fractionation of the acetone extract of the bark of Garcinia oblongifolia has resulted in the isolation of three new xanthones, oblongixanthones A-C (1-3), three new polyprenylated benzoylphloroglucinols, oblongifolins E-G (4-6), and 12 known compounds. Oblongifolins I (5) and J (6) are the first natural products that have similar structural features to those of two known oxidation products of garcinol. The structures of the new compounds 1-6 were characterized by spectroscopic data interpretation. All isolates were assayed for their apoptosis-inducing effects against HeLa-C3 cells. Oblongifolin C (16) was found to be the most potent apoptotic inducer of the compounds evaluated.

Cytotoxic ent-kaurane diterpenoids from Isodon henryi.

Chromatographic fractionation of the extract of Isodon henryi resulted in the isolation of seven new ENT-kaurane diterpenoids, named minheryins A-G (1-7), together with the six known ENT-kaurane diterpenoids leukamenin F (8), excisoidesin (9), leukamenin E (10), wangzaozin A (11), pseurata A (12), and racemosin A (13), which were elucidated by spectroscopic analysis. Compounds 7-13 were tested for their cytotoxicity against K562 and HepG2 cell lines, and they all exhibited significant activities with IC50 values<0.50 microg/mL. Isolates 1-5 were evaluated against the K562 cell line, and only 3 showed weak activity.

ent-Kaurane diterpenoids from Isodon scoparius.

Nine new ent-kaurane diterpenoids, isoscoparins D-L (1-9), and an artificial product, the acetonide of rabdoloxin A (10), along with 16 known analogues (11-26), were isolated from the leaves of Isodon scoparius. The new structures were determined by 1D and 2D NMR spectroscopic analysis. Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3, MCF-7, and SH-SY5Y cell lines.