Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126

The mangrove-sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126 was found to have productive piericidin metabolites featuring anti-renal cell carcinoma activities. In this study, in order to explore more diverse piericidin derivatives, and therefore to discover superior anti-tumor lead compounds, the NS126 strain was further fermented at a 300-L scale under optimized fermentation conditions. As a result, eight new minor piericidin derivatives (piericidins L-R (1–7) and 11-demethyl-glucopiericidin A (8)) were obtained, along with glucopiericidin B (9). The new structures including absolute configurations were determined by spectroscopic methods coupled with experimental and calculated electronic circular dichroism. We also proposed plausible biosynthetic pathways for these unusual post-modified piericidins. Compounds 1 and 6 showed selective cytotoxic activities against OS-RC-2 cells, and 2–5 exhibited potent cytotoxicity against HL-60 cells, with IC50 values lower than 0.1 μM. The new piericidin glycoside 8 was cytotoxic against ACHN, HL-60 and K562, with IC50 values of 2.3, 1.3 and 5.5 μM, respectively. The ability to arrest the cell cycle and cell apoptosis effects induced by 1 and 6 in OS-RC-2 cells, 2 in HL-60 cells, and 8 in ACHN cells were then further investigated. This study enriched the structural diversity of piericidin derivatives and confirmed that piericidins deserve further investigations as promising anti-tumor agents.

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Two new α-Methoxy-γ-Pyrones From the Mangrove Sediment-Derived Streptomyces psammoticus SCSIO NS126

Natural Product Communications ◽

10.1177/1934578x211041420 ◽

2021 ◽

Vol 16 (9) ◽

pp. 1934578X2110414

Author(s):

Kunlong Li ◽

Mengdie Zhou ◽

Ziqi Su ◽

Xiliang Yang ◽

Xuefeng Zhou ◽

...

Keyword(s):

Inhibitory Activity ◽

Spectroscopic Data ◽

Spectroscopic Analysis ◽

Mangrove Sediment ◽

Natural Sources ◽

Fermentation Conditions ◽

Acetylcholinesterase Inhibitory Activity ◽

Actinomycete Strain

Two new α-methoxy- γ-pyrone analogs, 2-methoxy-3-methyl-5,6-diethyl- γ-pyrone (2) and 2-methoxy-3,5-dimethyl-6-propyl- γ-pyrone (3), together with 2-methoxy-3,5-dimethyl-6-ethyl- γ-pyrone (1), firstly isolated from natural sources, were obtained from the EtOAc-solube extract of the mangrove sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126, under the optimized fermentation conditions. Their structures were elucidated by detailed spectroscopic analysis and by comparison of their spectroscopic data with those reported in the literature. Those α-methoxy-γ-pyrones were evaluated for their acetylcholinesterase inhibitory activity; however, none of them exhibited obvious activity. Moreover, their biosynthetic relationship with piericidins was also discussed.

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New Sulfoxide-Containing Derivatives from the Resin of Ferula sinkiangensis

Planta Medica ◽

10.1055/a-1495-5963 ◽

2021 ◽

Author(s):

Junchi Wang ◽

Haoli Yan ◽

Xiaoshuang Huo ◽

Lingyu Li ◽

Huijuan Wang ◽

...

Keyword(s):

Human Cancer ◽

Cytotoxic Activities ◽

Spectroscopic Methods ◽

Human Cancer Cell ◽

Addition Compound ◽

Human Cancer Cell Lines ◽

Nitric Oxide Release ◽

Tnf Α ◽

Ic50 Values ◽

Ferula Sinkiangensis

AbstractFour undescribed sulfoxide-containing derivatives, sinkiangenoxides A and B, (2Z, 4E)-sinkiangenoxide C, and (2E, 4E)-sinkiangenoxide C (1 – 4), and one known compound, 1-(methylthio)propyl (E)-1-propenyl disulfide (5), were isolated from the resin of Ferula sinkiangensis. Their structures were determined based on spectroscopic methods, including IR, UV, HRESIMS, NMR, and CD analysis. Compounds 2 – 4 showed moderate cytotoxic activities against four human cancer cell lines with IC50 values ranging from 15.0 to 40.3 µM. Sinkiangenoxide B (2) was shown to induce apoptosis in HepG2 cells. In addition, compound 5 effectively attenuated lipopolysaccharide-induced nitric oxide release and TNF-α, IL-1β, IL-6, and IL-10 expression.

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Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

Medicinal Chemistry ◽

10.2174/1573406416666200817164308 ◽

2020 ◽

Vol 16 ◽

Author(s):

Délis Galvão Guimarães ◽

Arlan de Assis Gonsalves ◽

Larissa Araújo Rolim ◽

Edigênia Cavalcante Araújo ◽

Victória Laysna dos Anjos Santos ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Biological Activities ◽

Supporting Electrolyte ◽

Cancer Cell Lines ◽

Molecular Structures ◽

Cytotoxic Activities ◽

Electrochemical Studies ◽

Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

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Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽

10.3390/biom11070957 ◽

2021 ◽

Vol 11 (7) ◽

pp. 957

Author(s):

Mamona Nazir ◽

Muhammad Saleem ◽

Muhammad Imran Tousif ◽

Muhammad Aijaz Anwar ◽

Frank Surup ◽

...

Keyword(s):

Amino Acids ◽

Secondary Metabolites ◽

Biological Effects ◽

Structural Diversity ◽

Chemical Diversity ◽

Biosynthetic Pathways ◽

Natural Sources ◽

Hybrid Compounds ◽

Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

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

Molecules ◽

10.3390/molecules26030739 ◽

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.

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Fusarins G–L with Inhibition of NO in RAW264.7 from Marine-Derived Fungus Fusarium solani 7227

Marine Drugs ◽

10.3390/md19060305 ◽

2021 ◽

Vol 19 (6) ◽

pp. 305

Author(s):

Guangyuan Luo ◽

Li Zheng ◽

Qilin Wu ◽

Senhua Chen ◽

Jing Li ◽

...

Keyword(s):

Fusarium Solani ◽

2D Nmr ◽

Inflammatory Activity ◽

Raw264.7 Cells ◽

Spectroscopic Methods ◽

X Ray ◽

X Ray Crystallography ◽

Structure Activity ◽

Ic50 Values ◽

New Compounds

Six new fusarin derivatives, fusarins G–L (1–6), together with five known compounds (5–11) were isolated from the marine-derived fungus Fusarium solani 7227. The structures of the new compounds were elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS, ECD, and ORC) and X-ray crystallography. Compounds 5–11 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide, with IC50 values ranging from 3.6 to 32.2 μM. The structure–activity relationships of the fusarins are discussed herein.

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Expanding the Structural Diversity of DNA Methyltransferase Inhibitors

Pharmaceuticals ◽

10.3390/ph14010017 ◽

2020 ◽

Vol 14 (1) ◽

pp. 17

Author(s):

K. Eurídice Juárez-Mercado ◽

Fernando D. Prieto-Martínez ◽

Norberto Sánchez-Cruz ◽

Andrea Peña-Castillo ◽

Diego Prada-Gracia ◽

...

Keyword(s):

Histone Deacetylases ◽

Dna Methyltransferase ◽

Structural Diversity ◽

Dna Methyltransferases ◽

Dna Methyltransferase Inhibitors ◽

Epigenetic Drug ◽

Ic50 Values ◽

Dietary Component ◽

Approved Drugs ◽

Epigenetic Processes

Inhibitors of DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug discovery. They are also chemical tools to understand the biochemistry of epigenetic processes. Herein, we report five distinct inhibitors of DNMT1 characterized in enzymatic inhibition assays that did not show activity with DNMT3B. It was concluded that the dietary component theaflavin is an inhibitor of DNMT1. Two additional novel inhibitors of DNMT1 are the approved drugs glyburide and panobinostat. The DNMT1 enzymatic inhibitory activity of panobinostat, a known pan inhibitor of histone deacetylases, agrees with experimental reports of its ability to reduce DNMT1 activity in liver cancer cell lines. Molecular docking of the active compounds with DNMT1, and re-scoring with the recently developed extended connectivity interaction features approach, led to an excellent agreement between the experimental IC50 values and docking scores.

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Rare Chromone Derivatives from the Marine-Derived Penicillium citrinum with Anti-Cancer and Anti-Inflammatory Activities

Marine Drugs ◽

10.3390/md19010025 ◽

2021 ◽

Vol 19 (1) ◽

pp. 25

Author(s):

Yi-Cheng Chu ◽

Chun-Hao Chang ◽

Hsiang-Ruei Liao ◽

Ming-Jen Cheng ◽

Ming-Der Wu ◽

...

Keyword(s):

A549 Cells ◽

Penicillium Citrinum ◽

Signaling Cascades ◽

Human Neutrophils ◽

Cytotoxic Activities ◽

Western Blot Assay ◽

Chromone Derivatives ◽

Anti Cancer ◽

Ic50 Values ◽

Induced Apoptosis

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC50 values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC50 values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.

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Cytotoxic Sesterterpenes from Thai Marine Sponge Hyrtios erectus

Marine Drugs ◽

10.3390/md16120474 ◽

2018 ◽

Vol 16 (12) ◽

pp. 474 ◽

Cited By ~ 7

Author(s):

Wirongrong Kaweetripob ◽

Chulabhorn Mahidol ◽

Pittaya Tuntiwachwuttikul ◽

Somsak Ruchirawat ◽

Hunsa Prawat

Keyword(s):

Methyl Ether ◽

Marine Sponge ◽

Indole Alkaloids ◽

Cytotoxic Activities ◽

Spectroscopic Methods ◽

The Absolute ◽

Modified Mosher’S Method

Four sesterterpenes, erectusolides B, C, D, and seco-manoalide-25-methyl ether, two 2-furanone derivatives, erectusfuranones A and B, together with thirteen known sesterterpenes, (6Z)-neomanoalide-24-acetate, two diastereomers of 24-O-methylmanoalide, luffariolide B, manoalide, (6E)- and (6Z)-neomanoalide, seco-manoalide, scalarafuran, 12-acetylscalarolide, 12-epi-O-deacetyl-19-deoxyscalarin, 12-epi-scalarin, and 12-O-deacetyl-12-epi-scalarin, three indole alkaloids, 5-hydroxy-1H-indole-3-carbaldehyde, hyrtiosine A, and variabine B, and one norterpene, cavernosine were isolated from the marine sponge Hyrtios erectus. Their structures were determined by means of spectroscopic methods and the absolute configurations of the asymmetric centers were determined using the modified Mosher’s method. The cytotoxic activities for the isolated compounds have been reported.

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Antioxidant, Cytotoxic Activities and Total Phenolic Content of Four Indonesian Medicinal Plants

Jurnal Kimia VALENSI ◽

10.15408/jkv.v2i4.267 ◽

2012 ◽

Vol 2 (4) ◽

Cited By ~ 1

Author(s):

Waras Nurcholis ◽

Bambang Pontjo Priosoeryanto ◽

Edy Djauhari Purwakusumah ◽

Takeshi Katayama ◽

Toshisada Suzuki

Keyword(s):

Free Radical ◽

Medicinal Plants ◽

Total Phenolic Content ◽

Phenolic Content ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Total Phenolic ◽

Cytotoxic Activities ◽

Ic50 Values ◽

Ethanol Extracts

The crude ethanol extracts of four Indonesian medicinal plants namely Curcuma xanthorrhiza Roxb.,Phyllanthus niruri Linn., Andrographis paniculata Ness., and Curcuma aeruginosa Roxb. wereexamined for their antioxidant (radical scavenging) activity using 2, 2-diphenyl-2-picrylhydrazyl(DPPH) free radical and cytotoxicity using brine shrimp lethality test (BSLT). The total phenoliccontent was used the Folin-Ciocalteu method. IC50 values for DPPH radical scavenging activityranged from 14.5 to 178.5 μg/ml, with P. niruri having the lowest value and therefore the mostpotent, and C. aeruginosa having the highest value. LC50 values for BSLT ranged from 210.3 to593.2 μg/ml, with C. xanthorrhiza and A. paniculata having the lowest and highest values,respectively. The total phenolic content of the Indonesian plants ranged from 133.0 ±3.7 to863.3±54.7 mg tannic acid equivalent per 1 g extract, with C. aeruginosa and P. niruri having thelowest and highest values, respectively. A positive correlation between free radical scavengingactivity and the content of phenolic compounds was found in the four of Indonesian medicinal plants.

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