scholarly journals Pyrenosetins A–C, New Decalinoylspirotetramic Acid Derivatives Isolated by Bioactivity-Based Molecular Networking from the Seaweed-Derived Fungus Pyrenochaetopsis sp. FVE-001

Marine Drugs ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 47 ◽  
Author(s):  
Bicheng Fan ◽  
Pradeep Dewapriya ◽  
Fengjie Li ◽  
Martina Blümel ◽  
Deniz Tasdemir
Keyword(s):  
Anticancer Activity ◽  
Marine Algae ◽  
Fucus Vesiculosus ◽  
Tetramic Acid ◽  
Molecular Networking ◽  
Ic50 Values ◽  
Ester Method ◽  
Ft Ir ◽  
Ft Ir Spectroscopy

Marine algae represent a prolific source of filamentous fungi for bioprospecting. In continuation of our search for new anticancer leads from fungi derived from the brown alga Fucus vesiculosus, an endophytic Pyrenochaetopsis sp. FVE-001 was selected for an in-depth chemical analysis. The crude fungal extract inhibited several cancer cell lines in vitro, and the highest anticancer activity was tracked to its CHCl3–soluble portion. A bioactivity-based molecular networking approach was applied to C18-SPE fractions of the CHCl3 subextract to predict the bioactivity scores of metabolites in the fractions and to aid targeted purification of anticancer metabolites. This approach led to a rapid isolation of three new decalinoylspirotetramic acid derivatives, pyrenosetins A–C (1–3) and the known decalin tetramic acid phomasetin (4). The structures of the compounds were elucidated by extensive NMR, HR-ESIMS, FT-IR spectroscopy, [α]D and Mosher’s ester method. Compounds 1 and 2 showed high anticancer activity against malignant melanoma cell line A-375 (IC50 values 2.8 and 6.3 μM, respectively), in line with the bioactivity predictions. This is the first study focusing on secondary metabolites of a marine-derived Pyrenochaetopsis sp. and the second investigation performed on the member of the genus Pyrenochaetopsis.

scholarly journals New Discorhabdin Alkaloids from the Antarctic Deep-Sea Sponge Latrunculia biformis

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 439 ◽  
Author(s):  
Li ◽  
Peifer ◽  
Janussen ◽  
Tasdemir
Keyword(s):  
Anticancer Activity ◽  
Deep Sea ◽  
Topoisomerase I ◽  
Active Sites ◽  
Binding Potential ◽  
Chemical Structures ◽  
Ic50 Values ◽  
Ft Ir ◽  
The Antarctic

The sponge genus Latrunculia is a prolific source of discorhabdin type pyrroloiminoquinone alkaloids. In the continuation of our research interest into this genus, we studied the Antarctic deep-sea sponge Latrunculia biformis that showed potent in vitro anticancer activity. A targeted isolation process guided by bioactivity and molecular networking-based metabolomics yielded three known discorhabdins, (−)-discorhabdin L (1), (+)-discorhabdin A (2), (+)-discorhabdin Q (3), and three new discorhabdin analogs (−)-2-bromo-discorhabdin D (4), (−)-1-acetyl-discorhabdin L (5), and (+)-1-octacosatrienoyl-discorhabdin L (6) from the MeOH-soluble portion of the organic extract. The chemical structures of 1–6 were elucidated by extensive NMR, HR-ESIMS, FT-IR, [α]D, and ECD (Electronic Circular Dichroism) spectroscopy analyses. Compounds 1, 5, and 6 showed promising anticancer activity with IC50 values of 0.94, 2.71, and 34.0 µM, respectively. Compounds 1–6 and the enantiomer of 1 ((+)-discorhabdin L, 1e) were docked to the active sites of two anticancer targets, topoisomerase I-II and indoleamine 2,3-dioxygenase (IDO1), to reveal, for the first time, the binding potential of discorhabdins to these proteins. Compounds 5 and 6 are the first discorhabdin analogs with an ester function at C-1 and 6 is the first discorhabdin bearing a long-chain fatty acid at this position. This study confirms Latrunculia sponges to be excellent sources of chemically diverse discorhabdin alkaloids.

scholarly journals A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

2021 ◽  
Vol 11 (19) ◽  
pp. 9139
Author(s):  
Maria Stefania Sinicropi ◽  
Cinzia Tavani ◽  
Camillo Rosano ◽  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Breast Cancer Cell Lines ◽  
Cellular Functions ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
In Silico Studies ◽  
Ic50 Values ◽  
Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

2021 ◽  
Vol 21 ◽  
Author(s):  
Nishtha Shalmali ◽  
Sandhya Bawa ◽  
Md Rahmat Ali ◽  
Sourav Kalra ◽  
Raj Kumar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Active Sites ◽  
Colorectal Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Adenocarcinoma Cells ◽  
Ic50 Values

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 µM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 µM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 µM and 106.91 µM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

scholarly journals 1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2324
Author(s):  
Danuta Branowska ◽  
Zbigniew Karczmarzyk ◽  
Ewa Wolińska ◽  
Waldemar Wysocki ◽  
Maja Morawiak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Estrogen Receptor Alpha ◽  
Theoretical Calculations ◽  
Molecular Structures ◽  
Breast Cancer Cell Lines ◽  
In Vitro Tests ◽  
Molecular Docking Study ◽  
Ic50 Values

In this study, we synthesized novel sulfonamides with a 1,2,4-triazine moiety according to pharmacophore requirements for biological activity. All the synthesized compounds were tested in vitro to verify whether they exhibited anticancer activity against the human breast cancer cell lines MCF-7 and MDA-MB-231. Among them, two most active ones, having IC50 values of 50 and 42 µM, respectively, were found to show higher anticancer activity than chlorambucil used as the reference in the in vitro tests. In addition, two other compounds, which had IC50 values of 78 and 91 µM, respectively, exhibited a similar level of activity as chlorambucil. X-ray analysis carried out for two of the compounds confirmed their synthesis pathway as well as their assumed molecular structures. Furthermore, a conformational analysis was performed, and electronic parameters of molecules were characterized using theoretical calculations at AM1 and DFT level. Moreover, molecular docking revealed the mode of binding of the investigated 1,2,4-triazine sulfonamides with the human estrogen receptor alpha (ERα).

scholarly journals A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5581
Author(s):  
Raju Suresh Kumar ◽  
Dhaifallah M. Al-thamili ◽  
Abdulrahman I. Almansour ◽  
Natarajan Arumugam ◽  
Faruq Mohammad
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
One Pot ◽  
Major Pathway ◽  
Molecular Scaffold ◽  
Highly Active ◽  
Ft Ir ◽  
Derivatives Of ◽  
Unique Mechanism

With an aim to develop more effective and affordable anticancer agents possessing a unique mechanism of action, we designed and synthesized derivatives of spirooxindole-pyrrolidine heterocyclic hybrids in good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 µg/mL concentration. The highly active molecular scaffold was tested for the in-depth mechanistic studies, and it was found that the major pathway of cell death is apoptosis which occurs through the induction of reactive oxygen species followed by the involvement of caspases.

Synthesis, in vitro inhibition effect of novel phthalocyanine complexes as carbonic anhydrase and paraoxonase enzyme inhibitors

2020 ◽  
Vol 24 (08) ◽  
pp. 1047-1053
Author(s):  
Emre Güzel ◽  
Barış Seçkin Arslan ◽  
Kübra Çıkrıkçı ◽  
Adem Ergün ◽  
Nahit Gençer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Enzyme Inhibitors ◽  
Inhibition Effect ◽  
H Nmr ◽  
Vis Spectroscopy ◽  
Ft Ir ◽  
First Time ◽  
Ft Ir Spectroscopy ◽  
C Nmr

The preparation and assessment of carbonic anhydrase and paraoxonase enzyme inhibition properties of 3-(2-(5-amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its nitrogen-containing non-peripheral phthalocyanine derivatives (3 and 4) are reported for the first time. The new phthalonitrile and its phthalocyanine derivatives have been elucidated by FT-IR spectroscopy, 1H-NMR, [Formula: see text]C-NMR, mass and UV-vis spectroscopy. The results demonstrated that all synthesized compounds moderately inhibited carbonic anhydrase and paraoxonase enzymes. Among the compounds, the most active ones were found to be compound 4 for PON (Ki : 0.14 [Formula: see text]M), compound 3 for hCA I (Ki : 22.52 [Formula: see text]M) and compound 1 for hCA II (Ki : 13.62 [Formula: see text]M).

scholarly journals Evaluation of Anticancer Activity of Olmesartan and Ramipril On A549 Cell Line

2018 ◽  
Vol 11 (3) ◽  
pp. 1351-1357 ◽  
Author(s):  
E Gayathri ◽  
K. Punnagai ◽  
D. Darling Chellathai
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Line ◽  
A549 Cell ◽  
Enzyme Inhibitor ◽  
A549 Cell Line ◽  
Ic50 Values

Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin II type 1 receptor antagonist (ARBs) are the most efficient cardiovascular drugs and exhibited efficient cytostatic activity in vitro in many malignant and normal cells1.OBJECTIVE: This study aims to assess the anticancer activity of these two drugs in a dose dependant manner using A549 cell line through MTT assay and Cell cycle analysis.. MATERIALS AND METHODS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle. The plates were read at 570 nm by using a PERCLIN ELMER (multimode reader). Measurements for concentration required for 50% inhibition was noted. RESULTS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle.

scholarly journals In-vitro Cytotoxicity and In-silico Insights of the Multi-target Anticancer Candidates from Haplophyllum tuberculatum

2021 ◽  
Vol 4 (3) ◽  
pp. 192-201
Author(s):  
Mosab Yahya Al-Nour ◽  
Ahmed H Arbab ◽  
Mohammad Khalid Parvez ◽  
Arwa Y Mohamed ◽  
Mohammed S Al-Dosari
Keyword(s):  
Hela Cell ◽  
Anticancer Activity ◽  
Cell Lines ◽  
In Vitro Cytotoxicity ◽  
Binding Modes ◽  
Web Servers ◽  
Hela Cell Lines ◽  
Ic50 Values ◽  
Haplophyllum Tuberculatum

This study aimed to investigate the anticancer activity of Haplophyllum tuberculatum(Forsk.) aerial parts ethanol extract and fractions and reveal the potential anticancer targets, binding modes, pharmacokinetics, and toxicity properties of its phytoconstituents. MTT assay was used to investigate the anticancer activity. TargetNet, ChemProt version 2.0, and CLC-Pred web servers were used for virtual screening, and Cresset Flare software was used for molecular docking with the 26 predicted targets. Moreover, pkCSM, swiss ADME, and eMolTox web servers were used to predict pharmacokinetics and safety. Ethanolic extracts of H. tuberculatum on HepG2 and HeLa cell lines showed promising activities with IC50 values 54.12 and 48.1 µg/mL, respectively. Further, ethyl acetate fraction showed the highest cytotoxicity on HepG2 and HeLa cell lines with IC50 values 41.7 and 52.31 µg/mL. Of 70 compounds screened virtually, polygamain, justicidin A, justicidin B, haplotubine, kusunokinin, and flindersine were predicted as safe anticancer drugs candidates. They showed the highest binding scores with targets involved in cell growth, proliferation, survival, migration, tumor suppression, induction of apoptosis, metastasis, and drug resistance. Our findings revealed the potency of H. tuberculatum as a source of anticancer candidates that further studies should support.

scholarly journals Green synthesis of silver nanoparticles by Aspergillus consortium and evaluating its anticancer activity against Human breast adenocarcinoma cell line (MCF7)

2017 ◽  
Vol 4 (1) ◽  
pp. 28 ◽  
Author(s):  
Rajeswari P. ◽  
Samuel P. ◽  
Vijayakumar J. ◽  
Selvarathinam T. ◽  
Sudarmani D.N.P. ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Anticancer Activity ◽  
Cell Line ◽  
Tamil Nadu ◽  
Breast Adenocarcinoma ◽  
Metallic Silver ◽  
Ic50 Values ◽  
Mcf7 Cell Line ◽  
Ft Ir ◽  
Cell Inhibition

Objective: The objective of the present study is to produce silver nanoparticles from marine fungi from south west coastal areas of Tamil Nadu and evaluating their potentials with special reference to anticancer activity.Methods: Hand core pushing technique is adapted to collect marine sediment samples along the coastal environs. Distinguished Aspergillus colonies were isolated and identified by wet mount procedure. The characterized Aspergillus consortium was subjected to produce silver nanoparticles. The extracellularly synthesized nanoparticles were characterized. Silver nanoparticles were evaluated for anticancer activity against MCF7 cell line by MTT assay. The IC50 values were determined.Results: Aspergillus consortium consist of A. niger, A. michelle and A. japonicus. Silver nanoparticles were extracellularly synthesized by the reduction of silver nitrate (AgNO3) to metallic silver (Ag+) ions results in the transformation of pale yellow to dark red colour. Constant shift was observed at 420 nm while monitoring the solution by UV-Vis spectrophotometer. The presence of important functional groups like –NH3 was confirmed by FT-IR Spectroscopy. Anticancer activity of the silver nanoparticles was evaluated against MCF7. There was 100% cell inhibition when concentration of the AgNPs reached 25 µg, 50 µg and 100 µg respectively in the test solution. Notably the IC50 value was found to be very lowest for the nanoparticles produced by A. japonicus and the value was found to be 1.47 µg/ml.Conclusions: Aspergillus consortium was found to be an ideal mycobiosystem for the production of silver nanoparticles with potential anticancer activity.

scholarly journals Production of exopolysaccharide by strains of Lactobacillus plantarum YO175 and OF101 isolated from traditional fermented cereal beverage

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5326 ◽  
Author(s):  
Adekemi Titilayo Adesulu-Dahunsi ◽  
Kumaraswamy Jeyaram ◽  
Abiodun Isiaka Sanni ◽  
Kolawole Banwo
Keyword(s):  
Lactobacillus Plantarum ◽  
Antioxidant Activities ◽  
Scale Up ◽  
Food Industries ◽  
Ft Ir ◽  
Experimental Values ◽  
Central Composite ◽  
Ft Ir Spectroscopy ◽  
Significant Factors

Lactobacillus plantarum YO175 and OF101 isolates from Nigerian traditional fermented cereal gruel ‘ogi’, were investigated on the basis of their capability to produce exopolysaccharide (EPS) on sucrose modified deMan Rogosa Sharpe medium (mMRS). Functional groups analysis of the EPSs produced (EPS-YO175 and EPS-OF101) by Fourier-transform infrared (FT-IR) spectroscopy revealed the presence of –OH, C=O and C–H groups. The chemical composition of EPS-YO175 and EPS-OF101 showed the presence of 87.1% and 80.62% carbohydrates and 1.21% and 1.47% protein. For maximum EPS yield, three significant factors were optimized using central composite design and response surface methodology, the predicted maximum EPS produced was 1.38 g/L and 2.19 g/L, while the experimental values were 1.36 g/L and 2.18 g/L for EPS-YO175 and EPS-OF101. The EPS samples showed strong antioxidant activities in-vitro. The scale-up of the production process of the EPS will find its potential application in food industries.

Sign in / Sign up

Export Citation Format

Share Document