Chemistry and biological activity of resin glycosides from Convolvulaceae species.

Carbohydrate-based drug discovery has gained more and more attention during the last few decades. Resin glycoside is a kind of novel and complex glycolipids mainly distributed in plants of the family Convolvulaceae. Over the last decade, a number of natural resin glycosides and derivatives have been isolated and identified, and exhibited a broad spectrum of biological activities, such as cytotoxic, multidrug-resistant reversal on both microbial pathogens and mammalian cancer cells, antivirus, anticonvulsant, antidepressant, sedative, vasorelaxant, laxative, and α-glucosidase inhibitory effects, indicating their potential as lead compounds for drug discovery. A systematic review of the literature studies was carried out to summarize the chemistry and biological activity of resin glycosides from Convolvulaceae species, based on various data sources such as PubMed, Web of Science, Scopus, and Google scholar. The keyword "Convolvulaceae" was paired with "resin glycoside," "glycosidic acid," "glycolipid," or "oligosaccharide," and the references published between 2009 and June 2021 were covered. In this article, we comprehensively reviewed the structures of 288 natural resin glycoside and derivatives newly reported in the last decade. Moreover, we summarized the biological activities and mechanisms of action of the resin glycosides with pharmaceutical potential. Taken together, great progress has been made on the chemistry and biological activity of resin glycosides from Convolvulaceae species, however, more exploratory research is still needed, especially on the mechanism of action of the biological activities.

Two New Indole Alkaloids from Toad Venom of Bufo bufo gargarizans.

Two new indole alkaloids, Bufotenidine B (2) and Bufocarboline A (6), along with seven known indole alkaloids (1, 3-5, and 7-9) and three organic acids (10-12), were isolated from the water extract of toad venom. The structures of the new alkaloids were elucidated by extensive spectroscopic methods. The absolute configurations of 4, 6, and 8 were determined for the first time by electronic circular dichroism (ECD) calculations. The cytotoxic activity of all compounds was tested against human malignant melanoma cells A375 by the MTT method, and no antitumor activity was observed.

New α-ditetralonyl glucoside from the green walnut husk of Juglans mandshurica.

One new α-ditetralonyl glucoside (1), was isolated from the green walnut husk of Juglans mandshurica (Juglandaceae), together with twelve known compounds (2-13). The structure of the new compound was determined as (2R,4S,10S,12S)-2-[7-(12,13,16-trihydroxy-α-tetralonyl-13-O-ß-D-glucopyranoside)]- 4,8-dihydroxy-α-tetralone-4-O-ß-D-glucopyranoside (1), on the basis of detailed spectroscopic analyses, and acidic hydrolysis. Compounds 6, 7 and 11 were isolated from the genus Juglans for the first time. Compound 1-13 showed weak cytotoxic against A549 and HeLa cell lines.

LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical.

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.

α-Tetralonyl Glucosides from the Green Walnut Husks of Juglans mandshurica and Their Antiproliferative Effects.

Two new α-tetralonyl glucosides, (4S)-4,5,8-trihydroxy-α-tetralone-5-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (1: ) and (4S)-4,8-dihydroxy-α-tetralone-4-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (2: ), together with eight known compounds (3:  - 10: ) were isolated from the green walnut husks of Juglans mandshurica. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS experiments. The isolated compounds were assayed for their cytotoxicity against two human cancer cell lines, A549 and HeLa. Four compounds (7:  - 10: ) exhibited inhibitory effects against two human cancer cell lines with GI50 values between 1.3 and 5.8 µM.

A mitochondria-targeted organic arsenical accelerates mitochondrial metabolic disorder and function injury.

Considering the vital role of mitochondria in the anti-cancer mechanism of organic arsenical, the mitochondria-targeted precursor PDT-PAO-TPP was designed and synthesized. PDT-PAO-TPP, as a delocalization lipophilic cation (DLCs) which mainly accumulated in mitochondria, contributed to improve anti-cancer efficacy and selectivity towards NB4 cells. In detail, PDT-PAO-TPP inhibited the activity of PDHC resulting in the suppression of ATP synthesis and thermogenesis disorder. Additionally, the inhibition of respiratory chain complex I and IV by short-time incubation of PDT-PAO-TPP also accelerated the respiration dysfunction and continuous generation of ROS. These results led to the release of cytochrome c and activation of caspase family-dependent apoptosis. Different from the mechanism of PDT-PAO in HL-60 cells, it mainly induced the mitochondrial metabolic disturbance resulting in the intrinsic apoptosis via inhibiting the activity of PDHC in NB4 cells, which also implied that the efficacy exertion of organic arsenical was a complex process involved in many aspects of cellular function. This study systematically clarifies the anti-cancer mechanism of mitochondria-targeted organic arsenical PDT-PAO-TPP and confirms the new target PDHC of organic arsenicals, which further supports the organic arsenical as a promising anticancer drug.

Zeasesquiterpene A-E, new sesquiterpenes from the roots of Zea mays.

Zeasesquiterpene A-E (1-5), five new sesquiterpenes with two cyclohexanes, were isolated from the roots of Zea mays. Their structures were elucidated on the basis of 1D and 2D NMR spectral data and ECD analysis. A plausible biosynthetic pathway for the compounds (1-6) were hypothesized. All isolated compounds were screened for cytotoxicities against five human cancer cell lines (A549, MDA-MB-231, SK-Hep-1, SNU638 and HCT116) in vitro by MTT assay. Compound 4 showed potential cytotoxic activities against A549 (14.3 µΜ) and SNU638 (9.7 µΜ). By contrast, compound 1 exhibited moderate cytotoxicity to the four human cancer cell lines (A549, SK-Hep-1, SUN638 and HCT116), and the IC50 values are from 19.5 µΜ to 22.5 µΜ.

A new indole alkaloid from the traditional Chinese medicine Chansu.

A new indole alkaloid N'-formylserotonin (1), along with five known indole alkaloids N'-methylserotonin (2), 5-hydroxy-1H-indole-3-carbaldehyde (3), N-acetylserotonin (4), 6-hydroxy-1-oxo-3,4-dihydro-ß-carboline (5), and bufoserotoin C (6), were isolated from the water extract of traditional Chinese medicine Chansu. Their structures were elucidated on the basis of spectral analyses. The cytotoxicities of 1-6 against human lung adenocarcinoma epithelial cells A549 were tested using the MTT method. Compound 6 exhibited stronger cytotoxic effect than 5-FU, and 1-5 showed no cytotoxic effects. Bufoserotonin C is one of the cytotoxic components in water-soluble extract of Chansu.

A New Indole Alkaloid from the Toad Venom of Bufo bufo gargarizans.

A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad. The cytotoxic activities of these compounds have been assayed against A375 and A549 cell lines by the MTT method; however, they showed no cytotoxic activities.