Discovery of new triterpenoids from Leptopus clarkei and their antiproliferative activity on cancer cells.

Two new triterpenoids (1-2), along with six known analogues (3-8) were obtained from the dried whole plant of Leptopus clarkei. Compound 1 is a 3,4-seco-lupane-type triterpenoid, and compound 2 is a phenylpropanoid-conjugated pentacyclic triterpenoid possessing trans-p-coumaroyl unit attached to oleanane-type skeleton. This is the first report on chemical investigation of the L. clarkei, and the triterpenoid derivatives were found in this plant for the first time. The structures of the new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. Additionally, the isolated compounds were evaluated for theircytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Notably, compound 2 exhibited the most significant antiproliferative activity with IC50 less than 20 µM for four cancer lines.

Naturally Occurring Polyhydroxylated Spirostanol Saponins, A Review of the Classification, Sources, Biosynthesis, Biological Activities, and Toxicity.

Polyhydroxylated spirostanol saponins, characterized by three or more hydroxy substitutions in the aglycone, have various interesting biological activities. In the present study, "steroids", "saponins", "polyhydroxylated", "spirostanol saponins", and "steroidal saponins" were used as search terms to screen the literature. Cited references were collected between 1950 and 2023 from the Web of Science, SciFinder, and China National Knowledge Internet (CNKI). A total of 407 polyhydroxylated spirostanol saponins were included in this review. These saponins were classified into three types, α, ß, and γ. Polyhydroxylated spirostanol saponins have potential benefits, primarily anti-inflammatory, antimicrobial, cytotoxic, and cAMP phosphodiesterase inhibitory activities. These compounds were found in 11 plant families and 36 genera. The top three families containing the most saponins were Asparagaceae, Melanthiaceae, and Amaryllidaceae, and the top five genera were Trillium, Helleborus, Allium, Dracaena, and Paris. The top five plants were Trillium tschonoskii Maxim., Ypsilandra thibetica Franch., Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz., Helleborus thibetanus Franch., and Helleborus foetidus L. On the basis of their diverse biological activities, these saponins and related plant resources are worthy of further development and utilization.

Carbazole alkaloids with potential cytotoxic activities targeted on PCK2 protein from Murraya microphylla.

From the 95% aqueous ethanol extract of Murraya microphylla, five pairs of new carbazole alkaloid enantiomers, (+/-)-microphylines N-R (1a/1b-5a/5b), were isolated, together with 20 known carbazole alkaloids. The structures of the new compounds were determined by the HRMS and NMR spectroscopic data, along with the calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. The known compound (+)-mahanine (21) showed significant cytotoxicities against Du145, HepG2, HeLa, and HCT-116 cell lines, and its possible mechanism was deduced to target on phosphoenolpyruvate carboxykinase 2 (PCK2) protein via surface plasmon resonance (SPR) and molecular docking.

Pyrrolizidine alkaloids from the seeds of Scleropyrum wallichianum.

Two new pyrrolizidine alkaloids, sclerwalins A and B (1 and 2), and one known 9-O-E-hydroxysenecioylretronecine (3) were first isolated from the seeds of Scleropyrum wallichianum. Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].

Cytotoxic secondary metabolites from the vulnerable conifer Cephalotaxus oliveri and its associated endophytic fungus Alternaria alternate Y-4-2.

Rare and endangered plants (REPs) and their associated endophytes survived in unique habitats are promising sources for natural product-derived drug discovery. In this study, six new (cephaloverines A-F, 1-6, resp.) and 16 known (11-26) cephalotaxine-type alkaloids, together with three new (oliverbiflavones A-C, 7-9, resp.) and 11 known (27-37) biflavonoids were isolated and characterized from the twigs and leaves of Cephalotaxus oliveri, an endangered plant endemic to China. Meanwhile, a preliminary investigation on the secondary metabolites from a selected fungal endophyte (i.e., Alternaria alternate Y-4-2) associated with the title plant led to the isolation of 21 structurally distinct polyketides including one new dimeric xanthone (10). The new structures (1-10) with the absolute configurations were determined by detailed spectroscopic analyses, electronic circular dichroism (ECD) or Na2MoO4-induced ECD, the modified Mosher's method, and some chemical transformations. Compounds 1-4 are the first representatives of naturally occurring N-oxides of cephalotaxine esters, while compounds 7-9 have a special structural feature of having a C-methylated biflavonoid skeleton. The Cephalotaxus alkaloids with ester side-chains at C-3 (1-6, 13-22, and 26) and four biflavonoids (27-29 and 34) were found to show pronounced cytotoxicities against a small panel of human cancer cell lines (A549, NCI-H460, HL60, NCI-H929, and RPMI-8226), with IC50 values mainly ranging from 0.003 to 9.34 µM. The most potent compound, deoxyharringtonine (16), generally exhibited IC50 values less than 10 nM. The structure-activity relationship (SAR) of the aforementioned Cephalotaxus alkaloids was briefly discussed.

Two new compounds from cultures of the basidiomycete Daedaleopsis tricolor.

Two new compounds, daedatrin K (1) and 2-hydroxy-1-(5-(hydroxymethyl)furan-2-yl)propan-1-one (2), were isolated from cultures of the basidiomycetes Daedaleopsis tricolor. The new structures were elucidated on the basis of extensive spectroscopic methods. At the same time, two compounds were tested for their cytotoxicities against five human cancer cell lines. [Formula: see text].

Synthesis and Antiproliferatory Activities Evaluation of Multi-Substituted Isatin Derivatives.

A series of multi-substituted isatin derivatives were synthesized using the powerful Sandmeyer reaction. The structures of these derivatives were confirmed by 1H-NMR, 13C-NMR, and HR-MS. Inhibition of proliferation activities of these derivatives against human leukemia cells (K562), human hepatocellular carcinoma cells (HepG2) and human colon carcinoma cells (HT-29) were evaluated in vitro using the MTT assay. Among the series, compound 4l exhibited strong antiproliferatory activities against K562, HepG2 and HT-29 cells with IC50 values of 1.75, 3.20, and 4.17 µM, respectively. The morphological, growth inhibitory and apoptosic effects of compound 4l in K562 cells, wound healing effect in HepG2 cells, and tube formating effect in matrix gel of HUVEC cells were evaluated consequently. All results indicated that compound 4l could be used as a potential antitumor agent in further investigations.

[Study on chemical constituents from Mastic (Pistacia lentiscus)].

Phytochemical investigation on the methanolic extract of Mastic by using various chromatographic techniques led to the isolation of 9 compounds. Based on the analysis of spectroscopic data(NMR and MS) and/or comparisons with the data reported in the literature, their structures were elucidated as 3ß,8α,13-trihydroxypolypoda-14-methoxy-14-methyl-17,21-diene(1), 4-hydroxymyrtenal(2),3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1, 2-diol(3), 2-oxo-Δ~3-4,5,5-trimethylcyclopentynyl acidic acid(4),(1S,2R,3R,5R)-6,6-dimethyl-4-methylidenebicyclo[3.1.1]-heptane-2,3-diol(5),(4R)-1-methyl-4-(1-hydroxyisopropyl)cyclohexene-6-one(6), 6,6-dimethyl-4-hydroxy[3.1.1]hept-2-ene-2-carboxylic acid(7), 6,6-dimethyl[3.1.1]hept-2-ene-2-carboxylic acid(8), 6,6-dimethyl-4-oxobicyclo[3.1.1]hept-2-ene-2-carboxylic acid(9). Compound 1 is a new compound and 2-9 were isolated from this species for the first time. In vitro cytotoxicity assay results indicated that compounds 1, 6 and 7 showed significant inhibitory effects against human lung cancer cell line A549 with IC_(50) values of 20.4, 25.1 and 22.5 µmoL·L~(-1).

Discovery of Bioactive Indole-Diketopiperazines from the Marine-Derived Fungus Penicillium brasilianum Aided by Genomic Information.

Identification and analysis of the whole genome of the marine-derived fungus Penicillium brasilianum HBU-136 revealed the presence of an interesting biosynthetic gene cluster (BGC) for non-ribosomal peptide synthetases (NRPS), highly homologous to the BGCs of indole-diketopiperazine derivatives. With the aid of genomic analysis, eight indole-diketopiperazines (1-8), including three new compounds, spirotryprostatin G (1), and cyclotryprostatins F and G (2 and 3), were obtained by large-scale cultivation of the fungal strain HBU-136 using rice medium with 1.0% MgCl2. The absolute configurations of 1-3 were determined by comparison of their experimental electronic circular dichroism (ECD) with calculated ECD spectra. Selective cytotoxicities were observed for compounds 1 and 4 against HL-60 cell line with the IC50 values of 6.0 and 7.9 µM, respectively, whereas 2, 3, and 5 against MCF-7 cell line with the IC50 values of 7.6, 10.8, and 5.1 µM, respectively.

(-)-Calcaridine B, a new chiral aminoimidazole-containing alkaloid from the marine sponge Leucetta chagosensis.

LC-DAD/MS-based dereplication of organic extract of a calcareous sponge Leucetta chagosensis afforded one new chiral aminoimidazole-containing alkaloid, (-)-calcaridine B (1), along with one achiral imidazole analog leucettamine E (2) as well as one known imidazole derivative (2E, 9E)-pyronaamidine-9-(N-methylimine) (3). Their structures were elucidated on the basis of NMR spectroscopic analyses, and comparing with the literature. The cytotoxic activities of all isolates were evaluated against three human cancer cell lines, and compounds 1 and 3 exhibited mild cytotoxicities toward the MCF-7 cell line with IC50 values of 25.3-24.2 µM, respectively.