scholarly journals Specific 12β-Hydroxylation of Cinobufagin by Filamentous Fungi

2004 ◽  
Vol 70 (6) ◽  
pp. 3521-3527 ◽  
Author(s):  
Min Ye ◽  
Guiqin Qu ◽  
Hongzhu Guo ◽  
Dean Guo
Keyword(s):  
Microbial Transformation ◽  
Reversed Phase ◽  
In Vitro Models ◽  
In Vitro Cytotoxicity ◽  
New Drugs ◽  
Hydroxyl Group ◽  
Cytotoxic Activities ◽  
Phase Liquid ◽  
New Compounds

ABSTRACT Biotransformation of natural products has great potential for producing new drugs and could provide in vitro models of mammalian metabolism. Microbial transformation of the cytotoxic steroid cinobufagin was investigated. Cinobufagin could be specifically hydroxylated at the 12β-position by the fungus Alternaria alternata. Six products from a scaled-up fermentation were obtained by silica gel column chromatography and reversed-phase liquid chromatography and were identified as 12β-hydroxyl cinobufagin, 12β-hydroxyl desacetylcinobufagin, 3-oxo-12β-hydroxyl cinobufagin, 3-oxo-12β-hydroxyl desacetylcinobufagin, 12-oxo-cinobufagin, and 3-oxo-12α-hydroxyl cinobufagin. The last five products are new compounds. 12β-Hydroxylation of cinobufagin by A. alternata is a fast catalytic reaction and was complete within 8 h of growth with the substrate. This reaction was followed by dehydrogenation of the 3-hydroxyl group and then deacetylation at C-16. Hydroxylation at C-12β also was the first step in the metabolism of cinobufagin by a variety of fungal strains. In vitro cytotoxicity assays suggest that 12β-hydroxyl cinobufagin and 3-oxo-12α-hydroxyl cinobufagin exhibit somewhat decreased but still significant cytotoxic activities. The 12β-hydroxylated bufadienolides produced by microbial transformation are difficult to obtain by chemical synthesis.

scholarly journals New Antiproliferative Triflavanone from Thymelaea hirsuta—Isolation, Structure Elucidation and Molecular Docking Studies

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 739
Author(s):  
Sameh S. Elhady ◽  
Reda F. A. Abdelhameed ◽  
Mayada M. El-Ayouty ◽  
Amany K. Ibrahim ◽  
Eman S. Habib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Tumors ◽  
Fold Increase ◽  
In Vitro Cytotoxicity ◽  
Mitogen Activated Protein Kinase ◽  
Wild Plant ◽  
Cytotoxic Activities ◽  
Ic50 Values ◽  
Thymelaea Hirsuta

In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

Halo-phenolic metabolites and their in vitro antioxidant and cytotoxic activities from the Red Sea alga Avrainvillea amadelpha

2021 ◽  
Vol 76 (5-6) ◽  
pp. 213-218
Author(s):  
Usama W. Hawas ◽  
Lamia T. Abou El-Kassem ◽  
Radwan Al-farawati ◽  
Fekri M. Shaher
Keyword(s):  
2D Nmr ◽  
Cytotoxic Activities ◽  
Dpph Radical ◽  
Srb Assay ◽  
Phenolic Metabolites ◽  
2D Nmr Spectra ◽  
New Compounds ◽  
Benzaldehyde Derivatives ◽  
Mcf 7

Abstract From the green alga Avrainvillea amadelpha, two new naturally halo-benzaldehyde derivatives were isolated by various chromatographic methods along with 10 known metabolites of bromophenols, sulfonoglycolipid, and steroids. Based on the 1D and 2D NMR spectra as well as on MS data, the structures of the new compounds were identified as 5-bromo-2-(3-bromo-4-hydroxybenzyl)-3,4-dihydroxybenzaldehyde named avrainvilleal (1), and 3-iodo-4-hydroxy-benzaldehyde (2). Using SRB assay, both compounds showed mild and weak cytotoxic activity against HeLa and MCF-7 cancer cell lines, compared to the good activity of their extract (IC50 values 3.1 and 4.3 μg/mL, respectively). However, avrainvilleal (1) displayed an effective scavenged DPPH radical activity with IC50 value 3.5 μM, compared to the antioxidant quercetin with IC50 value 1.5 μM.

Six New neo-Clerodane Diterpenoids from Aerial Parts of Scutellaria barbata and Their Cytotoxic Activities

Planta Medica ◽  
2018 ◽  
Vol 84 (17) ◽  
pp. 1292-1299 ◽  
Author(s):  
Guo-Chun Yang ◽  
Jia-Hui Hu ◽  
Bing-Long Li ◽  
Huan Liu ◽  
Jia-Yue Wang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Scutellaria Barbata ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Ic50 Values ◽  
Clerodane Diterpenoids

AbstractSix new neo-clerodane diterpenoids (1–6), scutebatas X – Z, A1-C1, along with twelve known ones (7–18) were obtained via the phytochemical investigation of the aerial parts of Scutellaria barbata. Their structures were established by detailed spectroscopic analysis. The absolute configurations of 1 and 2, as the representative members of this type, were identified based on a circular dichroic exciton chirality method. Moreover, in vitro cytotoxicity of compounds 1–6 were evaluated against three human cancer cell lines (SGC-7901, MCF-7, and A-549) using the MTT method. Compound 6 showed cytotoxic activities against all the three cell lines with IC50 values of 17.9, 29.9, and 35.7 µM, respectively.

scholarly journals Four New Pterosins from Pteris cretica and Their Cytotoxic Activities

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2767
Author(s):  
Jian Lu ◽  
Caiying Peng ◽  
Shuang Cheng ◽  
Jianqun Liu ◽  
Qinge Ma ◽  
...  
Keyword(s):  
Human Tumor ◽  
2D Nmr ◽  
Cytotoxic Activities ◽  
Aerial Parts ◽  
Pteris Cretica ◽  
Phytochemical Investigation ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
New Compounds

Phytochemical investigation of the aerial parts of Pteris cretica led to the isolation and elucidation of nine pterosins, including four new pterosins, creticolacton A (1), 13-hydroxy-2(R),3(R)-pterosin L (2), creticoside A (3), and spelosin 3-O-β-d-glucopyranoside (4), together with five known pterosins 5–9. Their structures were identified mainly on the basis of 1D and 2D NMR spectral data, ESI-MS and literature comparisons. Compounds 1 and 3 were new type of petrosins with a six membered ring between C-14 and C-15. The new compounds were tested in vitro for their cytotoxic activities against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Results showed that compounds 1 and 2 exhibited cytotoxic activity against HCT-116 cells with IC50 value of 22.4 μM and 15.8 μM, respectively.

Excavating Anticonvulsant Compounds from Prescriptions of Traditional Chinese Medicine in the Treatment of Epilepsy

2018 ◽  
Vol 46 (04) ◽  
pp. 707-737 ◽  
Author(s):  
Zefeng Zhao ◽  
Xirui He ◽  
Cuixia Ma ◽  
Shaoping Wu ◽  
Ye Cuan ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Therapeutic Strategy ◽  
In Vitro Models ◽  
New Drugs ◽  
Treatment Of Epilepsy ◽  
Effective Therapeutic Strategy ◽  
Promising Source

Traditional Chinese medicine (TCM) has a long history and been widely used in prevention and treatment of epilepsy in China. This paper is intended to review the advances in the active anticonvulsant compounds isolated from herbs in the prescription of TCM in the treatment of epilepsy. These compounds were introduced with the details including classification, CAS number specific structure and druggability data. Meanwhile, much of the research in these compounds in the last two decades has shown that they exhibited favorable pharmacological properties in treatment of epilepsy both in in vivo and in vitro models. In addition, in this present review, the evaluation of the effects of the anticonvulsant classical TCM prescriptions is discussed. According to these rewarding pharmacological effects and chemical substances, the prescription of TCM herbs could be an effective therapeutic strategy for epilepsy patients, and also could be a promising source for the development of new drugs.

scholarly journals Leishmanicidal and Cytotoxic Activities of Extracts and Naturally-Occurring Compounds from two Lauraceae Species

2011 ◽  
Vol 6 (2) ◽  
pp. 1934578X1100600
Author(s):  
Jeysson Sánchez-Suárez ◽  
Ericsson Coy-Barrera ◽  
Luis Enrique Cuca ◽  
Gabriela Delgado
Keyword(s):  
Leishmania Species ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Naturally Occurring ◽  
Ethanolic Extracts ◽  
Leishmania Panamensis ◽  
J774 Cells ◽  
Different Levels ◽  
Leishmania Parasites

The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis.

scholarly journals Computational toxicology

2015 ◽  
Vol 34 (12) ◽  
pp. 1304-1309 ◽  
Author(s):  
RT Naven ◽  
S Louise-May
Keyword(s):  
Critical Role ◽  
Pharmaceutical Research ◽  
In Vitro Models ◽  
New Drugs ◽  
Data Sets ◽  
Predictive Toxicology ◽  
Drug Induced ◽  
Chemical Toxicology

Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These ‘outliers’ and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them.

scholarly journals Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e6

2017 ◽  
Vol 21 (04-06) ◽  
pp. 354-363 ◽  
Author(s):  
Hui Chen ◽  
Stewart W. Humble ◽  
R. G. Waruna Jinadasa ◽  
Zehua Zhou ◽  
Alex L. Nguyen ◽  
...  
Keyword(s):  
Amino Acid ◽  
In Vitro Cytotoxicity ◽  
Chlorin E6 ◽  
New Compounds ◽  
Derivatives Of

Syntheses of three new chlorin e6 conjugates for PDT of tumors are reported. One of the new compounds 17 is conjugated with lysine at the 131-position, but the others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 152-conjugates (7–10), 131-monoconjugates 14, 16, and a 131,152-diconjugate 12 are reported. In vitro cytotoxicity experiments show that the 131-conjugates are more toxic than the 152-conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 131-ethylenediamine conjugate 11. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 152- and the 131,152-positions; these show high phototoxicity but relatively low dark toxicity compared with 11, and also the highest dark/photo cytotoxicity ratios.

scholarly journals Synthesis and Cytotoxicity of Thieno[2,3-b]Pyridine Derivatives Toward Sensitive and Multidrug-Resistant Leukemia Cells

2021 ◽  
Vol 68 (2) ◽  
pp. 458-465
Author(s):  
Salah A. Al-Trawneh ◽  
Amer H. Tarawneh ◽  
Anastassiya V. Gadetskaya ◽  
Ean-Jeong Seo ◽  
Mohammad R. Al-Ta’ani ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
In Vitro Cytotoxicity ◽  
Leukemia Cells ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Anti Cancer ◽  
Ic50 Values ◽  
New Compounds ◽  
Potential Use

A new series of substituted ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e were prepared by utilizing ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (1) and replacing of the 2-chlorine with anions obtained from phenol (2a), salicylaldehyde derivatives 2b–d or thiophenol (2e), leading to the respective ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e. The new compounds were evaluated for their in vitro cytotoxicity towards sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. The screening revealed that compounds 3a, 3b, and 3e inhibited the growth of both cell lines. Compound 3b, with a phenol moiety, exhibited the highest growth inhibitory activity against CEM/ADR5000 and CCRF-CEM cells with IC50 values 4.486 ± 0.286 and 2.580 ± 0.550 μM, respectively. Collectively, the presented results demonstrate that the synthesized thieno[2,3-b]pyridines warrant further exploration for potential use as anti-cancer agents.

scholarly journals Fractionation of Lycopodiaceae Alkaloids and Evaluation of Their Anticholinesterase and Cytotoxic Activities

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6379
Author(s):  
Aleksandra Dymek ◽  
Jarosław Widelski ◽  
Krzysztof Kamil Wojtanowski ◽  
Vladyslav Vivcharenko ◽  
Agata Przekora ◽  
...  
Keyword(s):  
Solvent System ◽  
Reversed Phase ◽  
Huperzine A ◽  
Process Conditions ◽  
Cytotoxic Activities ◽  
Ache Inhibitors ◽  
Methanolic Extracts ◽  
Silanized Silica ◽  
Vacuum Liquid Chromatography ◽  
New Compounds

In view of the abundant evidence that Lycopodiaceae alkaloids, including the well-known huperzine A (HupA), are among the potent acetylcholinesterase (AChE) inhibitors, an attempt was made to search for new compounds responsible for this property. For this purpose, three plant species belonging to the Lycopodiaceae family, commonly found in the Euro-Asia region, were subjected to the isolation of bioactive compounds, their identification and subsequent evaluation of their anticholinesterase and cytotoxic activities. Methanolic extracts of two Lycopodium and one Hupezia species were obtained via optimized pressurized liquid extraction (PLE) and then pre-purified using innovative gradient vacuum liquid chromatography (gVLC). For the first time, three sorbents of different porosity packed in polypropylene cartridges and mobile phase systems of different polarity were used to elute the target compounds. This technique proved to be a rapid tool for the obtainment of alkaloid fractions and allowed one to select the appropriate process conditions to yield potent AChE inhibitors in each of the species studied. More than 100 collected fractions were analyzed via HPLC/ESI-QTOF-MS, which enabled one to detect more than 50 compounds, including several new ones previously unreported. Some of them were present in high purity fractions (60–90% of the established purity). TLC bioautography assays proved that the analyzed species are rich sources of AChE inhibitors, but H. selago showed the highest anti-AChE activity. Additionally, the modified silanized silica gel sorbent used allowed one to isolate L. clavatum alkaloids more efficiently using an aqueous reversed-phase solvent system. Furthermore, the tested extracts from the three plant extracts were found to be safe, as they did not exhibit cytotoxicity to skin fibroblasts.

Sign in / Sign up

Export Citation Format

Share Document