In-vitro Cytotoxicity and Aromatase Inhibitory Activity of Flavonoids: Synthesis, Molecular Docking and In-silico ADME Prediction

2021 ◽  
Vol 21 ◽  
Author(s):  
Umang Shah ◽  
Samir Patel ◽  
Mehul Patel ◽  
Neeraj Jain ◽  
Nilesh Pandey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
In Vitro Cytotoxicity ◽  
Spectroscopic Techniques ◽  
Reference Drug

Background: Many natural and synthetic flavonoids have been studied and documented by inhibiting aromatase enzymes for their anti-cancer activity against breast carcinoma. The aromatase enzyme is a possible target for the estrogen's positive breast cancer receptor. Objective: Hence, a series of flavonoids have been synthesized and assessed for their in vitro cytotoxicity and aromatase inhibitory activity. Methods: 39 flavonoids were synthesized and characterized by spectroscopic techniques, and their computational study was performed using the maestro version of the Schrodinger. In-silico ADME properties were checked by QikPro software. A total of 18 compounds were evaluated based on the docking score using cytotoxicity assay in human breast cancer cell line MCF-7. Results: Of the 18 compounds tested, 07 compounds, namely 2b, 8b, 14b, 15b, 19b, 24b, and 30b flavonoids were found to be more active with their IC50 values of 20.73 μM, 1.636 μM, 16.08 μM, 22.02 μM, 15.75 μM, 0.345 μM and 16.08 μM, respectively, compared with the reference drug letrozole. The in-vitro aromatase inhibitory activity of six compounds 2b, 8b, 14b, 19b, 24b, and 30b was conducted using a fluorogenic assay kit. The values of IC50 for compounds 2b and 24b were found to be 0.31 μM and 0.36 μM, respectively. Conclusion: Therefore, it was concluded that compounds 2b and 24b had a potent inhibitory effect of aromatase compared with letrozole with an IC50 value of 0.86 μM. At the same time, the other compounds 8b, 14b, 30b, and 19b were considered to have similar aromatase inhibitory activity. Hence, their essential aromatase inhibitory activities make them good lead candidates for developing potent inhibitors of aromatase.

Fabrication of Calcium Sulfate Coated Selenium Nanoparticles and Corresponding In-Vitro Cytotoxicity Effects Against 4T1 Breast Cancer Cell Line

2021 ◽  
Author(s):  
Elnaz Faghfuri ◽  
Ramak Ajideh ◽  
Faranak Shahverdi ◽  
Mina Hosseini ◽  
Faranak Mavandadnejad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Calcium Sulfate ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
In Vitro Cytotoxicity ◽  
Selenium Nanoparticles ◽  
The Difference ◽  
Cytotoxicity Effects

Background: The inhibitory effect of selenium nanoparticles (SeNPs) on cancer cells has been reported in many studies. In this study, the purpose was to compare the in vitro effects of SeNPs and calcium sulfate coated selenium nanoparticles (CaSO4@ SeNPs) on breast cancer cells. Methods: CaSO4@SeNPs and SeNPs were chemically synthesized and characterized with Field Emission Scanning Electron Microscope (FESEM) and energy-dispersive X-ray spectroscopy (EDX). By applying MTT assay, the cytotoxicity effect of both nanomaterials on the 4T1 cancer cells was investigated. Results: While LD50 of SeNPs on 4T1 cancer cells was 80 µg, the LD50 of CaSO4@SeNPs was reported to be only 15 µg. The difference between the inhibition rates obtained for SeNPs and CaSO4@SeNPs was statistically significant (p=0.05). In addition, at higher concentrations (50 µg) of CaSO4@SeNPs, the cytotoxicity was 100% more than SeNPs alone.   Conclusion: According to the result of the present work, it can be concluded that de-coration of SeNPs with calcium sulfate leads to an increase in potency by decreasing the effective dose. This effect can be attributed to activation of intrinsic apoptosis signaling and/or pH regulatory properties of CaSO4@SeNPs. However, further studies are still needed to determine the exact corresponding mechanisms of this synergistic effect.

scholarly journals In Vitro Cytotoxicity of the Synthesized Gallic Acid Derivatives (N-Alkyl Gallamide) Against Breast MCF-7 Cancer Cells

2018 ◽  
Vol 34 (5) ◽  
pp. 2268-2272
Author(s):  
Maurin Marcelia ◽  
Ade Arsianti ◽  
Jilly Octaria Tagore Chan ◽  
Stevano Julio Wijoyo ◽  
Fadilah Fadilah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gallic Acid ◽  
Cytotoxic Effect ◽  
Linear Regression Analysis ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Tert Butyl ◽  
Ic50 Value ◽  
Mcf 7

Gallic acid is a phenolic compound distributed in plants and fruits which has been reported to have cytotoxic effect on MCF-7 breast cancer cell line. In this research, we investigated in vitro cytotoxic effect of six synthesized compounds of gallic acid derivatives (N-alkyl gallamide), namely N-methyl gallamide (2); N-ethyl gallamide (3); N-butyl gallamide (4); N-sec-butyl gallamide (5); N-tert-butyl gallamide (6) and N-hexyl gallamide (7) against breast MCF-7 cells by MTT assay. Linear regression analysis is utilized to analyze data to regenerate IC50 value. The results will be compared with gallic acid as an original compound and doxorubicin as a positive control.Among six synthesized compounds, N-tert-butyl gallamide (6) with IC50 value of 2.1 µg/mL, and N-hexyl gallamide (7) with IC50 value of 3.5µg/mL,showed the stronger cytotoxicity against breast MCF-7 cells compared to gallic acid and doxorubicin. Thus,N-tert-butyl gallamide (6) and N-hexyl gallamide (7) are potential to be further developed as a promising anti-breast cancer agents.

ZnO Nanoparticles Catalyst in the Synthesis of Bioactive Fused Pyrimidines as Anti-breast Cancer Agents Targeting VEGFR-2

2019 ◽  
Vol 15 (3) ◽  
pp. 277-286 ◽  
Author(s):  
Dina H. Dawood ◽  
Eman M.H. Abbas ◽  
Thoraya A. Farghaly ◽  
Mamdouh M. Ali ◽  
Mohammed F. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Inhibitory Activity ◽  
Antitumor Agents ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
Pharmaceutical Chemistry ◽  
Pyrimidine Derivatives ◽  
Zno Nps ◽  
Speed Up ◽  
Mcf 7

Background: Pyrimidines emerged as a remarkable class of heterocyclic compounds that have reinforced the pharmaceutical chemistry with various bioactive antitumor agents. Moreover, pyrimidine scaffold displayed VEGFR-2 inhibitory activity. Also, nano-sized catalysts are used in organic reactions in order to speed up the catalytic process. Objective: We were interested herein to synthesize a new series of fused pyrimidines using ZnO(NPs) to investigate their antitumor efficiency against breast MCF7 cancer and their VEGFR- 2 inhibition properties. Method: A simple and efficient method for the synthesis of fused pyrimidines was developed using zinc oxide nanoparticles ZnO(NPs) in refluxing ethanol. Results: The proposed structures of all new fused pyrimidines are in agreement with their spectral data. Antitumor evaluation of newly fused pyrimidine derivatives against breast MCF-7 cancer was performed. It was apparent that the 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a (IC50 = 9.12±1.16 µg/ml), 9c (IC50 = 9.10±1.07 µg/ml) and 9d (IC50 = 9.60±1.22 &µg/ml) exhibited equipotent antitumor activity as Tamoxifen (IC50 = 9.11±0.90 &µg/ml). Also, the inhibitory activity of the novel fused pyrimidine derivatives on VEGFR-2 as well as Tamoxifen was determined using breast cancer cell line MCF-7. The data was obvious that 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a, 9c and 9d exhibited noticeable VEGFR-2 inhibitory effect with % inhibition ranging from 80-84 % versus Tamoxifen 93.5%. Conclusion: We succeeded in this context to synthesize new fused pyrimidines using ZnO(NPs) as anti-breast cancer agents targeting VEGFR-2.<p&gt;

scholarly journals An In Silico and an In Vitro Inhibition Analysis of Glycogen Phosphorylase by Flavonoids, Styrylchromones, and Pyrazoles

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 306
Author(s):  
Sónia Rocha ◽  
Natália Aniceto ◽  
Rita C. Guedes ◽  
Hélio M. T. Albuquerque ◽  
Vera L. M. Silva ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Glycogen Phosphorylase ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Potent Inhibitory Effect ◽  
Key Enzyme ◽  
Experimental Findings

Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway. GP inhibitors are currently under investigation as a new liver-targeted approach to managing type 2 diabetes mellitus (DM). The aim of the present study was to evaluate the inhibitory activity of a panel of 52 structurally related chromone derivatives; namely, flavonoids, 2-styrylchromones, 2-styrylchromone-related derivatives [2-(4-arylbuta-1,3-dien-1-yl)chromones], and 4- and 5-styrylpyrazoles against GP, using in silico and in vitro microanalysis screening systems. Several of the tested compounds showed a potent inhibitory effect. The structure–activity relationship study indicated that for 2-styrylchromones and 2-styrylchromone-related derivatives, the hydroxylations at the A and B rings, and in the flavonoid family, as well as the hydroxylation of the A ring, were determinants for the inhibitory activity. To support the in vitro experimental findings, molecular docking studies were performed, revealing clear hydrogen bonding patterns that favored the inhibitory effects of flavonoids, 2-styrylchromones, and 2-styrylchromone-related derivatives. Interestingly, the potency of the most active compounds increased almost four-fold when the concentration of glucose increased, presenting an IC50 < 10 µM. This effect may reduce the risk of hypoglycemia, a commonly reported side effect of antidiabetic agents. This work contributes with important considerations and provides a better understanding of potential scaffolds for the study of novel GP inhibitors.

scholarly journals CYP-450 Mediated Herb-Drug Interactions of Ashwagandha and AYUSH-64 Used in COVID-19 Integrative Management: A Case Example of Remdesivir

2021 ◽  
Author(s):  
Siva Swapna Kasarla ◽  
Swapnil Borse ◽  
Yashwant Kumar ◽  
Neha Sharma ◽  
Madhu Dikshit
Keyword(s):  
Drug Interactions ◽  
Aqueous Extract ◽  
Inhibitory Activity ◽  
In Silico ◽  
Withania Somnifera ◽  
Inhibitory Effect ◽  
Inhibition Studies ◽  
Good Oral Bioavailability ◽  
Integrative Management

Abstract AimWithania somnifera Dunal (WS), known as Ashwagandha and AYUSH-64, a polyherbal formulation are repurposed for the management of COVID-19. The extensive use of these botanicals as home remedy along with other drugs for managing multifarious disease conditions is increasing over nations. This raises high chances of herb-drug interactions (HDIs) which may be beneficial, harmful, or even fatal. Therefore, current study aimed to explore the CYP mediated herb-drug interactions (HDIs) of Ashwagandha and AYUSH-64 along with case example of remdesivir to harness the best of these HDIs for integrative management of COVID-19Materials and MethodsThe aqueous extract of Ashwagandha and AYUSH-64 were characterized by LC-MS/MS. The in-silico pharmacokinetic (ADME) parameters were studied by using ADME tool. The in-vitro CYP-450 (CYP3A4, 2C8, 2D6) inhibition studies of WS and AYUSH-64 alone and in combination with a remdesivir were carried out resembling clinically scenario.ResultsTotal of 11 and 24 phytoconstituents were identified from the aqueous extract of Aswagandha and AYUSH-64. The in-silico ADME studies revealed that most of the phytoconstituents showed good oral bioavailability, drug likeliness, GI affinity and some of them displayed CYP-450 inhibitory activity. The in-vitro CYP-450 studies of remdesivir showed moderate inhibitory effect on CYP3A4, 2C8, 2D6. The aqueous extract of Aswagandha did not show any inhibitory activity towards all the studied CYP’s alone and in combination with remdesivir (IC50 >100µg/ml). Whereas, AYUSH-64 also followed the same trend but showed moderate inhibitory effect on CYP2C8 (IC50 <100µg/ml).ConclusionAswagandha did not exhibit HDIs with the CYP3A4, CYP2C8 and CYP2D6 thereby seem to be safe to co-administer with respective substrates. Whereas, AYUSH-64 only showed moderate HDIs towards CYP2C8 substrate among studied CYP enzymes. Caution is therefore warranted for prescribing AYUSH 64 along with CYP2C8 substrate drugs.

In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line

2019 ◽  
Vol 46 (6) ◽  
pp. 6361-6370 ◽  
Author(s):  
Bahman Moradipoodeh ◽  
Mostafa Jamalan ◽  
Majid Zeinali ◽  
Masood Fereidoonnezhad ◽  
Ghorban Mohammadzadeh
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
In Silico ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast

scholarly journals Biogenic Silver Nanoparticles: Assessment of Their Cytotoxicity, Genotoxicity and Study of Capping Proteins

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3022 ◽  
Author(s):  
Magdalena Wypij ◽  
Tomasz Jędrzejewski ◽  
Maciej Ostrowski ◽  
Joanna Trzcińska ◽  
Mahendra Rai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Silver Nanoparticles ◽  
Cell Line ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Synthesis Process ◽  
Mcf 7

The development of nanotechnology in the last two decades has led to the use of silver nanoparticles (AgNPs) in various biomedical applications, including antimicrobial, anti-inflammatory, and anticancer therapies. However, the potential of the medical application of AgNPs depends on the safety of their use. In this work, we assessed the in vitro cytotoxicity and genotoxicity of silver nanoparticles and identified biomolecules covering AgNPs synthesized from actinobacterial strain SH11. The cytotoxicity of AgNPs against MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264.7 was studied by MTT assay, cell LDH (lactate dehydrogenase) release, and the measurement of ROS (reactive oxygen species) level while genotoxicity in Salmonella typhimurium cells was testing using the Ames test. The in vitro analysis showed that the tested nanoparticles demonstrated dose-dependent cytotoxicity against RAW 264.6 macrophages and MCF-7 breast cancer cells. Moreover, biosynthesized AgNPs did not show a mutagenic effect of S. typhimurium. The analyses and identification of biomolecules present on the surface of silver nanoparticles showed that they were associated with proteins. The SDS-PAGE (sodium dodecyl sulfate–polyacrylamide gel electrophoresis) analysis revealed the presence of 34 and 43 kDa protein bands. The identification of proteins performed by using LC-MS/MS (liquid chromatography with tandem mass spectrometry) demonstrated their highest homology to bacterial porins. Capping biomolecules of natural origin may be involved in the synthesis process of AgNPs or may be responsible for their stabilization. Moreover, the presence of natural proteins on the surface of bionanoparticles eliminates the postproduction steps of capping which is necessary for chemical synthesis to obtain the stable nanostructures required for application in medicine.

scholarly journals Comparative Analysis of Pentacyclic Triterpenic Acid Compositions in Oleogum Resins of Different Boswellia Species and Their In Vitro Cytotoxicity against Treatment-Resistant Human Breast Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2153 ◽  
Author(s):  
Michael Schmiech ◽  
Sophia J. Lang ◽  
Katharina Werner ◽  
Luay J. Rashan ◽  
Tatiana Syrovets ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Cancer Cells ◽  
High Performance ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Treatment Resistant ◽  
Triterpenic Acids

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC50 of 8.3 ± 0.6 µg/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts.

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