Foegraecumoside O and P, a Pair of Triterpenoid Saponins with a 4/5/6 Fused Tricyclic Oleanane Carbon Skeleton from Lysimachia foenum-graecum Hance.

Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC50 at 12.4-19.2 µM in an MTT assay, comparing with the positive control doxorubicin, which had IC50 at 0.53-4.92 µM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed.

Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFRL858R/T790M mutation.

Dual- or multi-targeted EGFR inhibitors as single drugs can overcome EGFR inhibitor resistance and circumvent many disadvantages of combination therapy. In this work, fifteen 4-anilinoquinazoline derivatives bearing nitrogen mustard or hemi mustard moieties were designed and synthesized as dual EGFR-DNA targeting anticancer agents. Structures of target molecules were confirmed by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Compound 6g emerged as the most potent derivative against mutant-type H1975 cells with IC50 value of 1.45 µM, which exhibited 4-fold stronger potency than Chl/Gef (equimolar combination of chlorambucil and gefitinib). Kinase inhibition studies indicated that 6g showed excellent inhibitory effect on EGFRL858R/T790M enzyme, which was 8.6 times more effective than gefitinib. Mechanistic studies indicated that 6g induced apoptosis of H1975 cells in a dose-dependent manner and caused DNA damage. Importantly, 6g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of 6g inside EGFRWT and EGFRL858R/T790M binding sites. Moreover, 6g efficiently inhibited tumor growth in the H1975 xenograft model without side effects.

(±)-Corysaxicolaine A: a pair of antitumor enantiomeric alkaloid dimers from Corydalis saxicola.

(±)-Corysaxicolaine A (1), isolated from the aerial parts of Corydalis saxicola for the first time, is a pair of novel dimeric alkaloids, each of which is directly coupled by the rare 6, 12' C-C σ-bond between benzophenanthridine and protoberberine. The enantiomeric separation was achieved using chiral chromatography. Their structures, including stereochemistry, were clarified by carrying out extensive spectroscopic techniques and an electronic circular dichroism (ECD) calculation. (-)-Corysaxicolaine A was observed to exhibit an apparent cytotoxic effect against T24 cells with an IC50 value of 9.45 µM.

Extraction optimization, physicochemical characterization, and antioxidant activity of polysaccharides from Rhodosorus sp. SCSIO-45730.

Microalgal polysaccharides have been reported in many studies due to their uniqueness, biocompatibility, and high value, and Rhodosorus sp. SCSIO-45730 was an excellent source of polysaccharides and ß-glucans. However, the polysaccharides from the red unicellular alga Rhodosorus sp. SCSIO-45730 have barely been studied. In this work, hot water extraction of Rhodosorus sp. SCSIO-45730 polysaccharides (RSP) was optimized using response surface methodology (RSM) based on Box-Behnken design (BBD). The maximum RSP yield (9.29%) was achieved under the optimum extraction conditions: liquid-solid ratio of 50.00 mL g-1; extraction temperature of 84 °C; extraction time of 2 h; and extraction times of 5 times. The results of physicochemical characterization showed that RSP had high sulfate and uronic acid with content of 19.58% and 11.57%, respectively, rough layered structure, and mainly contained glucose, galactose, xylose, and galacturonic acid with mass percentages of 34.08%, 28.70%, 12.46%, and 12.10%. Furthermore, four kinds of antioxidant assays were carried out, and the results indicated that RSP had strong scavenging activities on ABTS and hydroxyl radical and moderate scavenging activities on DPPH and ferrous chelating ability. These results indicated that RSP showed potential as a promising source of antioxidants applied in food, pharmaceutical, and cosmetics industry. Supplementary Information: The online version contains supplementary material available at 10.1007/s10811-021-02646-2.

Platinum(IV) complexes conjugated with chalcone analogs as dual targeting anticancer agents: In vitro and in vivo studies.

For the sake to develop novel platinum(IV) complexes to reverse cisplatin (CDDP) resistence, four multifunctional platinum(IV) prodrugs via conjugating chalcones with the related platinum(IV) complexes derived from cisplatin were designed and evaluated for anti-tumor actyivities in vitro and in vivo. Among them, complex 9 exhibited excellent anticancer activities in vitro with IC50 values at the submicromolar level against the tested human cancer cells, whereas showed low cytotoxicity towards human normal liver cells HL-7702. Further mechanistic studies indicated that complex 9 induced G2/M phase arrest and apoptosis in A549 cells, which was associated with a collapse of the mitochondrial membrane potential (MMP), alterations in the expression of some apoptosis-related proteins, and enhanced level of the intracellular reactive oxygen species (ROS). More importantly, complex 9 significantly suppressed the tumor growth in the A549 xenograft model without obvious hints of toxicity.

Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs.

Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (TTP+) moiety, meant to specifically target them to tumor cells mitochondria, have been designed and synthesized. Among them, compound 2f possessed excellent antitumor activities against the tested human cancer cells, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than glycyrrhetinic acid and HCPT. Moreover, 2f significantly induced cell cycle arrest at the G2/M phase, and effectively inhibited cancer cells proliferation and migration. Mechanism studies revealed that 2f triggered apoptosis through the mitochondrial pathway via the collapse of mitochondrial membrane potential, reactive oxygen species production and the activation of caspase-9 and caspase-3.

Mappianines A-E, structurally diverse monoterpenoid indole alkaloids from Mappianthus iodoides.

Five previously undescribed monoterpenoid indole alkaloids, mappianines A-E, along with twelve known analogues, were isolated from the stems of Mappianthus iodoides Hand.-Mazz. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, and ECD calculations. The plausible biogenetic pathway of mappianine A was proposed. All the isolated compounds were evaluated for their cytotoxic effects on MGC-803, Bel-7404, A549, NCI-H460, and HepG2 cancer cell lines. Mappianine B, tetrahydroalstonine, ß-carbolin-1-one, and 1,2,3,4-tetrahydronorharman-1-one displayed moderate cytotoxicity against all cell lines tested, with IC50 values ranging from 5.19 to 42.86 µM.

Cytotoxic triterpenoid saponins from Lysimachia foenum-graecum.

Eleven oleanane-type triterpenoid saponins, foegraecumosides A-K, and eight known ones, were isolated from the aerial parts of Lysimachia foenum-graecum. Their structures were elucidated by spectroscopic data analyses and chemical methods. All isolated saponins were evaluated for their cytotoxicity against four human cancer cell lines (NCI-H460, MGC-803, HepG2, and T24). Seven saponins containing the aglycone cyclamiretin A exhibited moderate cytotoxicity against all tested human cancer cell lines, with IC50 values of 9.3-24.5 µM. Simultaneously, the cytotoxic activities of foegraecumosides A and B, lysichriside A, ardisiacrispins A and B, cyclaminorin, and 3-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranosyl-(1 â†’ 4)-α-l-arabinopyranosyl-cyclamiretin A were tested on drug-resistant lung cancer cell lines (A549 and A549/CDDP, respectively). Ardisiacrispin B displayed moderate cytotoxicity against A549/CDDP, with an IC50 value of 8.7 µM and a resistant factor (RF) of 0.9.

Antitumor lignanamides from the aerial parts of Corydalis saxicola.

BACKGROUND: Cancer is one of the leading cause of unnatural death globally. There is still a great need for effective anticancer agents from plant sources. Corydalis saxicola Bunting is a medicinal plant that is traditionally used to treat various diseases in southwest China. Previous phytochemical investigations of C. saxicola have focused on isoquinoline alkaloids that have been isolated, which have activity against anti-hepatitis B virus and inhibit DNA topoisomerase I. However, the exploration of other classes of constituents and their bioactivities needs further study. PURPOSE: The aim of this study was to investigate the antitumor activity of isolated lignanamides as well as their detailed cellular proliferation, suppression, and cytotoxic mechanisms. METHODS: Herbs were extracted and constituents were purified by chromatographic separation, including silica gel, ODS, MCI, Sephadex LH-20 and Preparative HPLC. The compound structures were elucidated by the use of UV, IR, NMR and MS spectral data. The cytotoxicity effects of all compounds from the MGC-803, HepG2, T24, NCI-H460, Spca-2, and HL-7702 cell lines were studied by MTT assays. The induction of apoptosis by corydalisin C was investigated using acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry. RESULTS: Three new lignanamides, together with five known analogues, were isolated from the aerial parts of C. saxicola. Corydalisin C possessed the most potent inhibitory effects, with an IC50 value of 8.81 ± 2.05µM against MGC-803 cells. SAR analysis showed that the sterics and chirality of lignanamides play a crucial role in pharmacologically relevant events. The antitumor activity was possibly due to the induction of cell apoptosis. Western blot experiments demonstrated that corydalisin C may induce apoptosis through both intrinsic and extrinsic apoptosis pathways, accompanied by down-regulating the expression of Bcl-2 and FasL in a time-dependent manner. CONCLUSION: This study provides evidence that a lignanamide from the ethyl acetate extract of whole plants of C. saxicola showing potential in cancer treatment.