Induction of Endoplasmic Reticulum Stress by Prodigiosin in Yeast Saccharomyces cerevisiae.

Prodigiosin, a red pigment produced by numerous bacterial species, exerts various antibiotic effects on prokaryotic and eukaryotic organisms. For instance, human carcinoma cell lines appear to suffer from endoplasmic reticulum (ER) stress in the presence of prodigiosin. Here, we demonstrated that prodigiosin also triggers the unfolded-protein response (UPR), which is a cytoprotective response against ER stress, in yeast Saccharomyces cerevisiae. An S. cerevisiae mutant carrying a UPR-deficient mutation was hypersensitive to prodigiosin. Our observations cumulatively indicate that protein folding in the ER is impaired by prodigiosin, illustrating a new mode of action.

Spermacosides a and B, two new triterpenoid saponins from Spermacoce ocymoides burm.f.

Two new triterpenoid saponins, named spermacosides A-B (1 - 2), together with two known oleanane-type triterpenoid saponins, 3-O-ß-D-xylopyranosyl-(1→3)-ß-D-glucopyranosylbayogenin (3) and 3-O-ß-D-glucopyranosylbayogenin (4), were isolated from the ethyl acetate extract of Spermacoce ocymoides Burm.f. in a phytochemical investigation. Their chemical structures were elucidated by spectroscopic data analysis (1D and 2D NMR, and HR-ESI-MS), as well as comparison with reported data. All these compounds were evaluated for inhibiting nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Among them, 1 showed a slight effect with an IC50 value of 108.65 ± 7.91 µM, and compounds 2-4 were inactive.

A new cucurbitane - type triterpenoid from the bark of Elaeocarpus hygrophilus Kurz.

A new cucurbitacin, 3ß-(ß-D-glucopyranosyloxy)-5ß,6ß:16α,23α-diepoxycucurbit-24-en-11-one or hygrocucurbin A (1), along with two known compounds, including 3ß-(ß-D-glucopyranosyloxy)-16α,23α-epoxycucurbita-5,24-dien-11-one (2) and (+)-lyoniresinol (3), were isolated from the bark of Elaeocarpus hygrophilus. Their chemical structures were elucidated by spectroscopic NMR, HR-IDA- TOF-MS analysis, and by comparison with the spectral data of corresponding compounds in the literature. Two cucurbitacins (1) and (2) were evaluated for their α-glucosidase inhibitory activity and cytotoxic against KB, MCF-7, Hep G2, and A549 cancer cell lines. For the α-glucosidase inhibitory activity, compound 1 showed an equivalent effect (IC50 197.4 ± 4.1 µM) compared to the acarbose, a positive control (IC50 208.5 ± 4.7 µM). And for the cytotoxicity, 2 was inactive while 1 was slightly sensitive against KB cells (IC50 233.3 ± 2.5 µM).

Identification and α-glucosidase inhibitory activity evaluation of two new coumarins derived from Mansonia gagei J. R. Drumm.

Five coumarins were isolated from the heartwood of Mansonia gagei, which included two newly discovered compounds, namely 11-hydroxypopulene E (1) and mansorin D (2), along with three previously identified compounds. The structures were determined through the utilisation of comprehensive spectroscopic data, ECD calculations, and a thorough comparison with existing literature data. The α-glucosidase inhibitory activities of all isolated compounds were assessed in yeast. Out of the compounds tested, compound 2 exhibited the most significant activity, displaying a percentage inhibition of 34.33% at a concentration of 200 µM.

Jasminanthoside - a new pregnane-steroid from Jasminanthes tuyetanhiae.

A new pregnane steroid, jasminanthoside (1), together with three known compounds, telosmoside A7 (2), syringaresinol (3), and methyl 6-deoxy-3-O-methyl-ß-D-allopyranosyl-(1→4)-ß-D-oleandropyranoside (4) were isolated from the ethyl acetate extract of Jasminanthes tuyetanhiae roots collected in Vietnam. Their chemical structures were elucidated by NMR and MS spectroscopic data analysis along with the comparison of their data with the published ones in the literature. Although 4 was a known compound, its full NMR data were reported for the first time. All isolated compounds, evaluated for their α-glucosidase inhibition, showed activities stronger than the positive control acarbose. Among them, 1 was the best with the IC50 value of 7.41 ± 0.59 µM.

Two new ent-kaurane-type diterpene diastereomers isolated from Coffea canephora.

Phytochemical investigation of the trunks of Coffea canephora yielded two new ent-kaurane diterpene diastereomers, which have been named coffecanepholide A, ent-3ß,16ß,17-trihydroxykauran-18-al (1) and coffecanepholide B, ent-3ß,16ß,17-trihydroxykauran-19-al (2). Structural elucidation and configurational assignment were deduced from extensive spectroscopic NMR/HRESIMS analysis and by comparison with the spectral data of the literature relevant structures. The isolated compounds were assayed for in vitro inhibitory activities against α-glucosidase. Structure 2 showed the α-glucosidase inhibitory activity with an IC50 value of 294.7 ± 0.9 µM, while compound 1 exhibited inactivity. In addition, the docking results revealed that structure 2 can form more interactions with amino acid residues at the active site of α-glucosidase, which gave a more negative binding energy (-9.56 kcal/mol) compared with 1 (-8.60 kcal/mol). This observation might be responsible for a better activity of 2 against α-glucosidase.

Hedyocoronins A and B: two new oleanane saponins from the aerial parts of Hedyotis coronaria.

Two new oleanane saponins, hedyocoronin A (1) and hedyocoronin B (2), were isolated from the aerial parts of Hedyotis coronaria (Kurz) Craib, Rubiaceae, collected at Da Oai district, Lam Dong province in Vietnam. Their chemical structures were elucidated by HR-MS, 1D and 2D-NMR spectra, along with the comparison with those reported in the literature. Compounds 1 and 2 showed weak cytotoxicity against KB and HeLa-S3 cancer cell lines with IC50 values of more than 54 µM.

Cafestol analogues from Coffea canephora: in vitro inhibition and molecular docking to α-glucosidase.

A new cafestol-type diterpenoid, 5ß-hydroxy-2-oxocafestol named coffecanepholide C (1) along with three known diterpenoids including cafestol (2), tricalysiolide A (3) and atractyligenin (4) were identified from the Coffea canephora trunks collected at Lam Dong province, Vietnam. Their structures were elucidated by HRESIMS and NMR spectroscopic analysis (1H, 13C, COSY, HSQC, HMBC, and NOESY NMR) as well as compared with data in the literature. Upon evaluation of the α-glucosidase inhibitory activity, compound 1 (IC50 = 142.0 ± 0.2 µM) and compound 3 (IC50 = 286.2 ± 1.2 µM) exhibited activity against α-glucosidase, while structures 2 and 4 showed no activity. Furthermore, the docking simulations revealed that the carbonyl groups of compounds 1 and 3 formed hydrogen bonds with Lys506 residue at the enzyme pocket, which may induce the α-glucosidase inhibitory activity.

Study on the Anticancer Activity of Prodigiosin from Variants of Serratia Marcescens QBN VTCC 910026.

Prodigiosin (Pg), a secondary metabolism produced by numerous bacterial species, is known as anticancer, antibacterial, antifungal, immunosuppressant, antioxidant, antimalarial properties. Pg has been tested for antitumor activity in many different cancer cell lines but studies in LU-1, KB cell lines, and tumor-bearing mice are still limited. In this study, Serratia marcescens QBN VTCC 910026 strain (GenBank: KX674054.1) was mutated using Ethyl Methanesulfonate (EMS) to increase the production of Pg. One strain known as EMS 5 was capable of increasing prodigiosin biosynthetic yield by 52% when compared to the wild-type strain. Red bacterial pigmented colonies containing Pg were collected from solid media, lysed with acetone, purified with toluene: ethyl acetate at a ratio of 9: 1 (v/v), and then used to evaluate the potential anticancer activity. The purity of Pg was confirmed using a high-performance liquid chromatography (HPLC) method which indicated a 98% rate. Pg chemical formula which was determined using 1H-NMR and 13C-NMR spectroscopy, confirmed as prodigiosin (Pg). Human breast cancer cell lines MCF-7, oropharyngeal cancer KB, and particularly lung cancer LU-1 in vitro were used to test the anticancer activity of purified Pg compound. It showed a strong inhibitory ability in all the cancer cell lines. Furthermore, the isolated Pg had capable of inhibiting tumor growth, the tumor volume decreased by 36.82%, after 28 days. The results indicated that the bacterial prodigiosin from variants Serratia marcescens QBN VTCC 910026 strain is an encouraging fragment suitable for therapeutic applications.

Reticulatin, a novel C43-spiroterpenoid from the lichen Parmotrema reticulatum growing in Vietnam.

A novel C43-spiroterpenoid, reticulatin (1), was isolated from the lichen Parmotrema reticulatum (Taylor) M. Choisy (Parmeliaceae). Five previously-reported compounds were also isolated: zeorin (2), leucotylin (3), lupeol (4), betulinic acid (5), and dihydroreynosin (6). The structures were elucidated by 1D, 2D NMR, and HRESIMS spectroscopy and comparison with the literature. We propose that reticulatin is a biosynthetic product of fusicoccadiene and vinapraesorediosic acid A via Diels-Alder addition. Reticulatin is the first C43-spiroterpenoid identified from lichen metabolites. All compounds were evaluated for inhibition of α-glucosidase. Compound 1 showed the most potent inhibition, with an IC50 value of 3.90 µM, much lower than that of the acarbose positive control (IC50 165 µM).

A new diphenyl ether from Parmotrema indicum Hale growing in Vietnam.

Chemical investigation of the lichen Parmotrema indicum Hale led to the isolation of one new diphenyl ether, parmetherine D (1), along with eight known compounds (2-9). The structures were determined by analysis of MS and NMR data and by comparison with the literature. Compounds 1, 2, and 7 were evaluated for α-glucosidase inhibition. Only compound 1 exhibited significant inhibition.[Formula: see text].

Three quinolinone alkaloid - phenylpropanoid adducts from Melicope pteleifolia.

Preliminary in vitro cytotoxic test on different extracts of Melicope pteleifolia collected at Dak Nong province, Vietnam showed that the n-hexane one was the most potent. From this n-hexane extract, three new quinolinone alkaloid-phenylpropanoid derivatives (1-3) and three known compounds (4-6) were isolated. Based on NMR and HR-MS analysis, their chemical structures were elucidated as melicoptines A-C (1-3), flindersine (4), 3,4,5-trimethoxybenzoic acid (5) and (24S)-methylcholestan-1α,3ß-diol (6). Isolated compounds (1-4) were evaluated for their anti-bacterial and cytotoxic activities against human non-small cell lung cancer (A549), human cervical cancer (HeLa), human Burkitt's lymphoma (Raji) and normal fibroblasts (NIH-3T3). All of them were inactive.

Usneaceratins A and B, two new secondary metabolites from the lichen Usnea ceratina.

Two new compounds, comprising one dibenzofuran, named usneaceratin A (1), and one phenolic acid, named usneaceratin B (2), together with one known dibenzofuran, isousnic acid (3), and two known phenolics, orsellinic acid (4) and methyl orsellinate (5) were clarified from the lichen Usnea ceratina using variously chromatographic methods. Their structures were testified by comprehensive HR-ESI-MS, and NMR spectroscopic analysis, and comparison with published data. Their α-glucosidase inhibitory activity of all compounds was measured. Usneaceratin B (2) possessed better inhibition against α-glucosidase enzyme (IC50 value of 41.8 µM) than the standard drug acarbose (IC50 value of 214.50 µM).

A new oleanane-skeleton triterpene isolated from Coffea canephora.

Extensive fractionation of n-hexane extract from the dried powdered-trunks of Coffea canephora Pierre ex A.Froehner (Rubiaceae) led to the isolation of a new oleanane-skeleton triterpene, coffecanolic acid (1), along with three known analogues sumaresinolic acid (2), oleanolic acid (3), and 3-O-acetyloleanolic acid (4). The chemical structures were elucidated using FT-IR, 1D and 2D NMR and HR-ESI-MS data analysis. The isolated compounds were assayed for in vitro α-glucosidase inhibitory activity by determining their half-maximal inhibitory concentration (IC50, µM). Compounds 1-4 exhibited higher inhibitory activities when compared with acarbose, a positive control. Compound 1 was found to be the most potent molecule against α-glucosidase, with the IC50 = 83.0 ± 1.2 µM, which improved by 2.5-fold over acarbose (IC50 = 209.8 ± 0.3 µM) in this assay.[Formula: see text].

Ricicomin A, a new alkaloid from the leaves of Ricinus communis Linn.

From the leaves of Ricinus communis Linn., one new alkaloid, named ricicomin A (1) together with three known ones, ricinine (2), N-demethylricinine (3) and 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (4) were justified by repeated chromatographic methods. Their structures were determined by comprehensive IR, HR-ESI-MS and NMR analyses. Compound 4 was identified for the first time from the genus Ricinus. DFT-NMR chemical shift calculations and subsequent DP4+ probability methods were applied to confirm the chemical structure of 1. Compounds 1-3 did not display cytotoxic effect against three human cancer cell lines (MCF-7, HepG2 and HeLa) using SRB assay.

Further terpenoids from Euphorbia tirucalli.

The phytochemical investigation of Euphorbia tirucalli L. (Euphorbiaceae) yielded four new compounds, including a rare cadalene-type sesquiterpene (tirucadalenone), two tirucallane triterpenoids, euphorol L and euphorol M, with the latter being described as an epimeric mixture, and a euphane triterpene, namely, euphorol N, together with 7 known compounds. Their structures and absolute configurations were elucidated from analysis of 1D (1H, J-modulated 13C) and 2D NMR (HSQC, HMBC and NOESY), high-resolution mass spectrometry (HRESIMS), optical rotation, and GIAO NMR shift calculation followed by CP3 analysis, along with comparison with literature reports. All these compounds were tested for cytotoxicity against K562, MCF-7 and/or and HepG2 tumor cell lines. Only tirucadalenone displayed a mild cytotoxic activity.

Two new triterpenoids from the roots of Phyllanthus emblica.

Two new triterpenes, the seco-friedelane type secofriedelanophyllemblicine and the ursane-derived saponin ursophyllemblicoside were isolated from the roots of the edible fruit-producing Phyllanthus emblica. Their structures were unambiguously elucidated using extensive 1D and 2D NMR analyses, high resolution mass spectrometry and single-crystal X-ray crystallographic analyses along with comparison with literature data. Secofriedelanophyllemblicine represents the first 3,4-secofriedelane bearing a carboxylic acid group substituent at C-20. Ursophyllemblicoside, incorporating the rare 21α hydroxyursolic acid as a sapogenol represents the first example of saponin comprising this aglycone. Secofriedelanophyllemblicine displayed a moderate cytotoxicity against K562 and HepG2 cancer cell lines.