Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity.

ABSTRACT: Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase (SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3?- and 17?-hydroxyl steroids. Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17?-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-?-glucosides (AT-17?-Gs) and acetylated estradiol-17-O-?-glucosides (AE-17?-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 3'-acetylated testosterone17-O-?-glucoside towards seven human tumor cell lines were thus observable.

SUBMITTER: Liu M

PROVIDER: S-EPMC6251810 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Steroidal Glycosides from Convallaria majalis Whole Plants and Their Cytotoxic Activity.

Project description:Phytochemical examination of Convallaria majalis (Liliaceae) whole plants yielded 15 steroidal glycosides (1-15), including nine new compounds (4-6, 10-15) with a lycotetrose unit. The structures of the new compounds were determined using two-dimensional Nuclear magnetic resonance (NMR) analyses and chemical methods. The isolated compounds were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, and HSC-4 and HSC-2 human oral squamous cell carcinoma cell lines. Of these, (25S)-spirost-5-en-3?-yl O-?-d-glucopyranosyl-(1?2)-O-[?-d-xylopyranosyl-(1?3)]-O-?-d-glucopyranosyl-(1?4)-?-d-galactopyranoside (1) exhibited cytotoxic activity against HL-60, A549, HSC-4, and HSC-2 cells with IC50 values ranging from 0.96 to 3.15 ?M. The corresponding furostanol glycoside of 1, (25S)-26-[(?-d-glucopyranosyl)oxy]-22?-hydroxyfurost-5-en-3?-yl O-?-d-glucopyranosyl-(1?2)-O-[?-d-xylopyranosyl-(1?3)]-O-?-d-glucopyranosyl-(1?4)-?-d-galactopyranoside (8), was cytotoxic to the adherent cell lines of A549, HSC-4, and HSC-2 cells with IC50 values of 2.97, 11.04, and 8.25 ?M, respectively. The spirostanol lycotetroside (1) caused necrotic cell death in A549 cells in a dose-dependent manner. Alternatively, the furostanol lycotetroside (8) induced apoptotic cell death in A549 cells in a time-dependent manner, as was evident by morphological observations and flow cytometry analyses.

| S-EPMC5713327 | biostudies-literature

Three New Cytotoxic Steroidal Glycosides Isolated from Conus pulicarius Collected in Kosrae, Micronesia.

Project description:Three new sulfated steroidal glycosides (3-5), along with known cholesterol derivatives (1,2), were isolated from the visceral extract of the cone snail Conus pulicarius. The structure of each new compound was elucidated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The three new compounds exhibited significant in vitro cytotoxicity (GI50 values down to 0.49 ?M) against the K562 human leukemia cell line.

| S-EPMC5742839 | biostudies-other

Enzymatic Biosynthesis of Simple Phenolic Glycosides as Potential Anti-Melanogenic Antioxidants.

Project description:Simple phenolics (SPs) and their glycosides have recently gained much attention as functional skin-care resources for their anti-melanogenic and antioxidant activities. Enzymatic glycosylation of SP aglycone make it feasible to create SP glycosides with updated bioactive potentials. Herein, a glycosyltransferase (GT)-encoding gene was cloned from the fosmid libraries of Streptomyces tenjimariensis ATCC 31603 using GT-specific degenerate PCR followed by in silico analyses. The recombinant StSPGT was able to flexibly catalyze the transfer of two glycosyl moieties towards two SP acceptors, (hydroxyphenyl-2-propanol [HPP2] and hydroxyphenyl-3-propanol [HPP3]), generating stereospecific α-anomeric glycosides as follows: HPP2-O-α-glucoside, HPP2-O-α-2″-deoxyglucoside, HPP3-O-α-glucoside and HPP3-O-α-2″-deoxyglucoside. This enzyme seems not only to prefer UDP-glucose and HPP2 as a favorable glycosyl donor and acceptor, respectively but also differentiates the positional difference of the hydroxyl function as acceptor catalytic sites. Paired in vitro and in vivo antioxidant assays represented SPs and their corresponding glycosides as convincing antioxidants in a time- and concentration-dependent manner by scavenging DPPH radicals and intracellular ROS. Even compared to the conventional agents, HPP2 and glycoside analogs displayed improved tyrosinase inhibitory activity in vitro and still suppressed in vivo melanogenesis. Both HPP2 glycosides are further likely to exert the best inhibitory activity against elastase, eventually highlighting these glycosides with enhanced anti-melanogenic and antioxidant activities as promising anti-wrinkle hits.

| S-EPMC9312196 | biostudies-literature

In Vivo Hepatoprotective and Nephroprotective Activity of Acylated Iridoid Glycosides from Scrophularia hepericifolia.

Project description:Phytochemical investigation of the chloroform fraction obtained from Scrophularia hypericifolia aerial parts led to the isolation of nine acylated iridoid glycosides. The new compounds were identified as 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl-6'-acetyl catalpol (6'-acetyl hypericifolin A) (1), 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl-6'-acetyl catalpol (6'-acetyl hypericifolin B) (2), 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin A) (3) and 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin B) (4). Previously reported compounds were identified as laterioside (5), 8-O-acetylharpagide (6), 6-O-α-L(4'-O-trans-cinnamoyl) rhamnopyranosyl catalpol (7), lagotisoside D (8) and harpagoside (9). Identification achieved via analyses of physical and spectral data including 1D, 2D NMR and High Resolution Electrospray Ionization Mass spectroscopy (HRESIMS). Compounds 2-4 and 6 were subjected to biological evaluation against paracetamol-induced toxicity. The biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) as well as total bilirubin were used to access the liver condition. Measurement of serum levels of urea, creatinine, sodium and potassium cations were indicators for kidney condition. Liver and kidney samples were subjected to histopathological study. The best protection was found in the group treated with 3 followed by 4 and 6, while 2 was almost inactive.

| S-EPMC7918105 | biostudies-literature

Steroidal and pregnane glycosides from Ypsilandra thibetica

Project description:The whole plants of Ypsilandra thibetica have been analyzed as part of a systematic study on saponin constituents of medicinal plants. This has resulted in the isolation of two new bisdesmosidic furostanol saponins, named ypsilandroside P (1) and ypsilandroside Q (2), and one new pregnane glycoside, named ypsilandroside R (3), together with nine known steroidal glycosides. Their structures were elucidated on the basis of extensive spectroscopic analysis, including that of 2D NMR data, and the results of acidic hydrolysis. Ypsilandroside P (1) was cytotoxicity against two human tumor cell lines. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-011-0039-z and is accessible for authorized users.

| S-EPMC4131569 | biostudies-literature

Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines.

Project description:Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes.

| S-EPMC6273349 | biostudies-literature

Two new acylated flavonol glycosides from the seeds of Lepidium sativum.

Project description:Two new acylated flavonol glycosides named kaempferol-3-O-(2-O-sinapoyl)-β-D-galactopyranosyl-(1 → 2)-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside (1) and quercetin-3-O-(6-O-benzoyl)-β-D-glucopyranosyl-(1 → 3)-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside (2), were isolated together with six known compounds from the seeds of L. sativum. Their structures were elucidated on the basis of spectroscopic analysis and chemical methods. In vitro 1 and 2 inhibited nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values of 25.36 and 25.08 µM, respectively.

| S-EPMC6271768 | biostudies-literature

Novel Steroidal Glycosides from the Bulbs of Lilium pumilum.

Project description:Examination of the bulbs of Lilium pumilum (Liliaceae) led to the isolation of four novel steroidal glycosides (1-4) with a 2,3,4-trisubstituted ?-d-glucopyranosyl unit. In 1 and 3, the ?-L-arabinopyranosyl moiety is linked to C-3 of the inner trisubstituted ?-D-glucopyranosyl group and is present as an usual ?C? conformation. In contrast, in 2 and 4, the ?-L-arabinopyranosyl moiety, which is attached to C-4 of the inner trisubstituted ?-D-glucopyranosyl group, is present as a ¹C? conformation. The structures of the new steroidal glycosides were determined based on the results of spectroscopic analyses, including two-dimensional (2D) NMR data and hydrolysis.

| S-EPMC6331790 | biostudies-literature

Enzymatic synthesis of epothilone A glycosides.

Project description:Epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. The in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (YjiC) from Bacillus licheniformis generated six novel epothilone A glycoside analouges including epothilone A 7-O-β-D-glucoside, epothilone A 7-O-β-D-galactoside, epothilone A 3,7-O-β-D-digalactoside, epothilone A 7-O-β-D-2-deoxyglucoside, epothilone A 7-O-β-L-rhamnoside, and epothilone A 7-O-β-L-fucoside. Epothilone A 7-O-β-D-glucoside was structurally elucidated by ultra-high performance liquid chromatography-photo diode array (UPLC-PDA) conjugated with high resolution quantitative time-of-flight-electrospray ionization mass spectroscopy (HR-QTOF ESI-MS/MS) supported by one-and two-dimensional nuclear magnetic resonance studies whereas other epothilone A glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The time dependent conversion study of epothilone A to epothilone A 7-O-β-D-glucoside found to be maximum (~26%) between 3 h to 5 h incubation.

| S-EPMC4052672 | biostudies-literature

Cytotoxic Polyhydroxysteroidal Glycosides from Starfish Culcita novaeguineae.

Project description:Four new polyhydroxysteroidal glycosides-culcinosides A-D (1, 2, 4, and 7)-along with three known compounds-echinasteroside C (3), linckoside F (5), and linckoside L3 (6)-were isolated from the ethanol extract of starfish Culcita novaeguineae collected from the Xisha Islands of the South China Sea. The structures of new compounds were elucidated through extensive spectroscopic studies and chemical evidence, especially two-dimensional (2D) NMR techniques. The cytotoxicity of the new compounds against human glioblastoma cell lines U87, U251, and SHG44 were evaluated.

| S-EPMC5867636 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data