scholarly journals Chemical Constituents from Artemisia annua and Vitex agnus-castus as New Aromatase Inhibitors: In-vitro and In-silico Studies

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Hend M. Dawood ◽  
Eman Shawky ◽  
Hala M. Hammoda ◽  
Aly M. Metwally ◽  
Reham S. Ibrahim
Keyword(s):  
Aromatase Inhibitors ◽  
Inhibitory Activity ◽  
Artemisia Annua ◽  
Chemical Constituents ◽  
Interaction Patterns ◽  
In Silico Studies ◽  
Agnus Castus ◽  
Ic50 Values ◽  
Trimethyl Ether

Abstract. Aromatase inhibitors are important in certain cancers such as breast cancer in postmenopausal women. In this study, eight constituents from Artemisia annua L. and Vitex agnus-castus L. were isolated and evaluated for their aromatase inhibitory activity using in-vitro fluorimetric assay. All tested compounds possessed moderate to strong inhibitory activity with β-sitosterol and myricetin-3,7,4'-trimethyl ether  being the most active with IC50 values of 0.13 and 0.25 μM, respectively. Compounds were subjected to induced fit docking (IFD) where β-sitosterol, possessed comparable interaction patterns to the natural co-crystallized ligand androstenedione.  Furthermore, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME&T)‎ properties of the compounds were evaluated revealing that all compounds' properties - except some of β- sitosterol related to solubility - lied within the acceptable range for human use, thereby considered as competent drug-like molecules. These findings could qualify β- sitosterol, myricetin-3,7,4'-trimethyl ether and domesticoside   as lead compounds for the development of new aromatase inhibitors.

scholarly journals Two new compounds from leaves of Bruguiera cylindrica (L.) Blume with the in vitro α-glucosidase inhibitory activity

2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Thuy Thi Le Nguyen ◽  
Tung Thanh Bui ◽  
Phung Kim Phi Nguyen ◽  
Chi Minh Tran ◽  
Tu Dang Cam Phan ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Ethyl Acetate Extract ◽  
Chemical Constituents ◽  
Positive Control ◽  
Chemical Structures ◽  
Ic50 Values ◽  
Bruguiera Cylindrica ◽  
New Compounds ◽  
Better Than

Introduction: Bruguiera cylindrica is one of the mangrove plants belonging to Bruguiera genus. This genus is characterized by the presence of a large number of compounds, but the research on bioactivities has not been investigated so far. In the present research, the α-glucosidase inhibitory activity, as well as chemical constituents of the ethyl acetate extract of this plant, were studied. Methods: The chemical structures of two new compounds were elucidated by spectroscopic and computational methods. Results: Two new compounds, benzobrugierol (1) and bruguierine (2), were isolated from leaves of Bruguiera cylindrica (L.) Blume, together with nine known ones, including lupeol (3), betulin (4), chrysoeriol (5), glut-5-ene-3-ol (6), cholesta-4-ene-3-one (7), 3α-(Z)-coumaroyllupeol (8), 3α-(E)-coumaroyllupeol (9), 3β-hydroxycholesta-5-ene-7-one (10) and β-sitosterol 3-O-β-D-glucopyranoside (11). Extracts and some isolated compounds were evaluated for α-glucosidase inhibitory activities. Conclusion: The results showed that most of the extracts and tested compounds exhibited activities better than the positive control acarbose, especially two new compounds 1 and 2 with their IC50 values of 17.9 ± 0.4 and 34.6 ± 0.7 (mg/mL), respectively.

scholarly journals New Carbonic Anhydrase-II Inhibitors from Marine Macro Brown Alga Dictyopteris hoytii Supported by In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7074
Author(s):  
Kashif Rafiq ◽  
Ajmal Khan ◽  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Majid Khan ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inhibitory Activity ◽  
2D Nmr ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Binding Behavior ◽  
In Silico Studies ◽  
Ic50 Values ◽  
First Time

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds (1–12) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate (3), dimethyl 2,6-dibromoterepthalate (4), and (E)-3-(4-(dimethoxymethyl)phenyl) acrylic acid (5) are isolated for the first time as a natural product, while the rest of the compounds (1, 2, 6–12) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1H, 13C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds (13–20) previously isolated by our group from the same source along with the currently isolated compounds (1–12) were screened against the CA-II enzyme. All compounds, except 6, 8, 14, and 17, were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds (1, 4, 5, 7, 9, 10, 12, 13, 15, 18, and 19) exhibited significant inhibitory activity against CA-II with IC50 values ranging from 13.4 to 71.6 μM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

scholarly journals In Vitro and In Silico Studies of Soluble Epoxide Hydrolase Inhibitors from the Roots of Lycopus lucidus

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 356
Author(s):  
Yoo Kyong Han ◽  
Ji Sun Lee ◽  
Seo Young Yang ◽  
Ki Yong Lee ◽  
Young Ho Kim
Keyword(s):  
Inhibitory Activity ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
In Silico Studies ◽  
Allosteric Sites ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Ic50 Values ◽  
Dimethyl Lithospermate ◽  
Lycopus Lucidus

Soluble epoxide hydrolase (sEH) is an enzyme that is considered a potential therapeutic target in human cardiovascular disease. Triterpenes (1–4) and phenylpropanoids (5–10) were isolated from Lycopus lucidus to obtain sEH inhibitors through various chromatographic purificationtechniques. The isolated compounds were evaluated for their inhibitory activity against sEH, and methyl rosmarinate (7), martynoside (8), dimethyl lithospermate (9) and 9″ methyl lithospermate (10) showed remarkable inhibitory activity, with the IC50 values ranging from 10.6 ± 3.2 to 35.7 ± 2.1 µM. Kinetic analysis of these compounds revealed that 7, 9 and 10 were competitive inhibitors bound to the active site, and 8 was the preferred mixed type inhibitor for allosteric sites. Additionally, molecular modeling has identified interacting catalytic residues and bindings between sEH and inhibitors. The results suggest that these compounds are potential candidates that can be used for further development in the prevention and treatment for cardiovascular risk.

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Thiazole-Dihyrofuran Derivatives as Aromatase Inhibitors

2021 ◽  
pp. 105123
Author(s):  
Derya Osmaniye ◽  
Şennur Görgülü ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Aromatase Inhibitors ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies

scholarly journals Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2211
Author(s):  
Thitinan Aiebchun ◽  
Panupong Mahalapbutr ◽  
Atima Auepattanapong ◽  
Onnicha Khaikate ◽  
Supaphorn Seetaha ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Kinase Inhibitor ◽  
Kinase Assay ◽  
Vinyl Sulfone ◽  
Egfr Tyrosine Kinase ◽  
In Silico Studies ◽  
Sulfone Derivatives

Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC50 value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC50 values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.

scholarly journals Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110166
Author(s):  
Xin Yi Lim ◽  
Janice Sue Wen Chan ◽  
Terence Yew Chin Tan ◽  
Bee Ping Teh ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Rna Binding ◽  
Symptomatic Relief ◽  
Andrographis Paniculata ◽  
Spike Protein ◽  
Rapid Review ◽  
In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

scholarly journals Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1694
Author(s):  
Kamel Arraki ◽  
Perle Totoson ◽  
Alain Decendit ◽  
Andy Zedet ◽  
Justine Maroilley ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Methanolic Extract ◽  
Significant Inhibition ◽  
Isolation And Identification ◽  
Vasorelaxant Effect ◽  
Methanolic Extracts ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
First Time

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.

scholarly journals Antiglycation potential of Indigoferin a, Indigoferin B and Indigoferin C natural products from Indigofera heterantha Brandis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ayesha Khan ◽  
Ajmal Khan ◽  
Manzoor Ahmad ◽  
Mumtaz Ali ◽  
Umar Farooq ◽  
...  
Keyword(s):  
Natural Products ◽  
Diabetic Complications ◽  
Inhibitory Activity ◽  
Chemical Constituents ◽  
Intramolecular Hydrogen Bonding ◽  
Glycation End Products ◽  
End Products ◽  
Serious Disease ◽  
Intramolecular Hydrogen

Abstract Background Diabetes is a long-lasting and serious disease that effect in worldwide individual lives, families, and societies. Hyperglycemia of diabetes mellitus produced Advance Glycation End Products that are associated with diabetic complications like neuropathy, nephropathy, retinopathy, and cardiovascular diseases. Methods In this study, the natural products isolated from of Indigofera heterantha Brandis, Indigoferin A (S1), Indigoferin B (S2) and Indigoferin C (S3) were evaluated for their in vitro antiglycation activity. Results The compounds exhibited a significant inhibitory activity against the formation of Advanced Glycation End-Products with IC50 values of 674.25 ± 3.2 μM, 407.03 ± 4.7 μM and 726.41 ± 2.1 μM, respectively. Here, important structure-activity relationship was observed, when the intramolecular hydrogen bonding interactions suppressed the antiglycation activity of compound S3. Thus, the study clearly demonstrates that the number and the position of substituents act as an assisting factor and directly influence the inhibitory activity of the natural product by altering the sugar or protein binding affinity. Conclusions This study explain first time the antiglycation inhibitory ability of chemical constituents isolated from I. heterantha and can be used for above late diabetic complications.

scholarly journals Aktivitas Penghambatan Xantin Oksidase pada Ekstrak Daun Sirih Hitam (Piper sp)

2016 ◽  
Vol 3 ◽  
pp. 160-163
Author(s):  
Muhammad Amir Masruhim ◽  
Wisnu Cahyo Prabowo ◽  
Dita Paramitha
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Betel Leaf ◽  
Activity Test ◽  
Ic50 Values ◽  
One Way Anova

Hyperuricemia is a condition in which increased levels of uric acid in the blood. Xanthine oxidase role in the oxidation of hypoxanthine and xanthine to uric acid. One treatment of hyperuricemia is inhibiting xanthine oxidase in the process of formation of uric acid. The purpose of this study to determine the inhibitory activity of xanthine oxidase in the ethanol extract of black betel leaf (Piper sp). Xanthine oxidase inhibitory activity test using UV-Vis spectrophotometry in vitro with a concentration of 5 ppm, 10 ppm and 20 ppm. The data obtained were analyzed using one-way ANOVA. The result is the ethanol extract of black betel leaf has a different activity significantly and IC50 values obtained is 65.96 ppm.

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