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.

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 IN VITRO ANTIPLASMODIAL AND CYTOTOXIC ACTIVITIES OF A SUNGKAI (PERONEMA CANESCENS) LEAF EXTRACT

2018 ◽  
Vol 10 (10) ◽  
pp. 109
Author(s):  
Jhons Fatriyadi Suwandi ◽  
Mahardika Agus Wijayanti ◽  
Mustofa .
Keyword(s):  
Plasmodium Falciparum ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Selectivity Index ◽  
Antiplasmodial Activity ◽  
Cytotoxic Activities ◽  
Aqueous Extracts ◽  
Diphenyltetrazolium Bromide ◽  
Ic50 Values

Objective: The aim of this study was to assess the antiplasmodial and cytotoxic activities and to evaluate the selectivity indices of acetone, ethanol and aqueous extracts of Peronema canescens leaves.Methods: Antiplasmodial activity was measured in vitro against Plasmodium falciparum strains D10 and FCR3 by 72 h incubation at 37 °C in a candle jar. Parasitaemia was calculated by counting the parasite numbers in thin smears. In vitro cytotoxicity was assayed in Vero cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and reading the absorbency at 595 nm with an ELISA reader. The assessed parameters included: 50% inhibitory concentration (IC50) of antiplasmodial activity, IC50 of cytotoxic activity and the selectivity index of the Peronema canescens leaf extract.Results: The IC50 values for the acetone, ethanol and aqueous extracts were 26.33±1.65, 37.96±8.17 and 12.26±1.05 μg/ml, respectively, against the Plasmodium falciparum D10 strain and 51.14±8.65, 70.22±14.13 and 34.85±6.04 μg/ml, respectively, against the FCR3 strain. For Vero cells, the IC50 values for the acetone, ethanol and aqueous extracts were 23.37±5.63, 629.46±24.85 and 634.00±144.82 μg/ml, respectively. The selectivity indices of these extracts were 0.89, 16.46 and 51.70, respectively, for the D10 strain and 0.46, 8.90 and 18.00, respectively, for the FCR3 strain.Conclusion: The aqueous extract of Peronema canescens leaves had the highest in vitro antiplasmodial activity and the best selectivity index.

scholarly journals In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 728
Author(s):  
Alberto Aragón-Muriel ◽  
Yamil Liscano ◽  
Yulieth Upegui ◽  
Sara M. Robledo ◽  
María Teresa Ramírez-Apan ◽  
...  
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Lanthanide Complexes ◽  
Human Tumor ◽  
Model Membranes ◽  
Leishmania Braziliensis ◽  
Cytotoxic Activities ◽  
Schiff Base Ligands ◽  
Major Interest

Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

scholarly journals Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 208
Author(s):  
Ahlam Elwekeel ◽  
Dalia El Amir ◽  
Enas I. A. Mohamed ◽  
Elham Amin ◽  
Marwa H. A. Hassan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Flavonoid Glycosides ◽  
Total Phenolic ◽  
Cytotoxic Activities ◽  
Alcoholic Extract ◽  
Molecular Docking Study

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

scholarly journals In-vitro Cytotoxicity and in silico Molecular Docking of Alkaloids from Tiliacora acuminata

2020 ◽  
Vol 54 (2s) ◽  
pp. s295-s300
Author(s):  
Jeswiny Rodrigues ◽  
Kirankumar Hullatti ◽  
Sunil Jalalpure ◽  
Pukar Khanal
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
In Vitro Cytotoxicity ◽  
In Silico Molecular Docking

scholarly journals Derivatization of Rosmarinic Acid Enhances its in vitro Antitumor, Antimicrobial and Antiprotozoal Properties

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1078 ◽  
Author(s):  
Silvia Bittner Fialová ◽  
Martin Kello ◽  
Matúš Čoma ◽  
Lívia Slobodníková ◽  
Eva Drobná ◽  
...  
Keyword(s):  
Rosmarinic Acid ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Phosphonium Salts ◽  
Ros Scavenging ◽  
Ic50 Values ◽  
Quaternary Phosphonium Salts

On its own, rosmarinic acid possesses multiple biological activities such as anti-inflammatory, antimicrobial, cardioprotective and antitumor properties, and these are the consequence of its ROS scavenging and inhibitory effect on inflammation. In this study, two quaternary phosphonium salts of rosmarinic acid were prepared for the purpose of increasing its penetration into biological systems with the aim of improving its antimicrobial, antifungal, antiprotozoal and antitumor activity. The synthetized molecules, the triphenylphosphonium and tricyclohexylphosphonium salts of rosmarinic acid, exhibited significantly stronger inhibitory effects on the growth of HCT116 cells with IC50 values of 7.28 or 8.13 μM in comparison to the initial substance, rosmarinic acid (>300 μM). For the synthesized derivatives, we detected a greater than three-fold increase of activity against Acanthamoeba quina, and a greater than eight-fold increase of activity against A. lugdunensis in comparison to rosmarinic acid. Furthermore, we recorded significantly higher antimicrobial activity of the synthetized derivatives when compared to rosmarinic acid itself. Both synthetized quaternary phosphonium salts of rosmarinic acid appear to be promising antitumor and antimicrobial agents, as well as impressive molecules for further research.

scholarly journals Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2766 ◽  
Author(s):  
Heba E. Hashem ◽  
Abd El-Galil E. Amr ◽  
Eman S. Nossier ◽  
Elsayed A. Elsayed ◽  
Eman M. Azmy
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Topoisomerase Iv ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Cytotoxicity Studies ◽  
Ic50 Values

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

In Vitro Human Dihydroorotate Dehydrogenase Inhibitory, Anti-inflammatory and Cytotoxic Activities of Alkaloids from the Seeds of Nigella glandulifera

Planta Medica ◽  
2018 ◽  
Vol 84 (14) ◽  
pp. 1013-1021 ◽  
Author(s):  
Jun-Bo Gao ◽  
Xing-Jie Zhang ◽  
Rui-Han Zhang ◽  
Li-Li Zhu ◽  
De-Bing Pu ◽  
...  
Keyword(s):  
Folk Medicine ◽  
Positive Control ◽  
Cytotoxic Activities ◽  
Dihydroorotate Dehydrogenase ◽  
X Ray Diffraction ◽  
Ic50 Values ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds ◽  
First Time

AbstractFour new dolabellane-type diterpene alkaloids, glandulamines A – D (1 – 4), together with twelve known compounds (5 – 16), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures of 1 – 16 were elucidated based on NMR data analysis, HRMS experiments and other spectroscopic interpretations. The absolute configuration of 5 was determined by single-crystal X-ray diffraction data for the first time. Compounds 10 and 12 showed human dihydroorotate dehydrogenase inhibitory activity with IC50 values of 61.1 ± 5.3 and 45.9 ± 3.0 µM, respectively. Molecular docking of the active compound 12 and positive control teriflunomide on the inhibitor-binding site of human dihydroorotate dehydrogenase was subsequently performed to visualize the interaction pattern. In addition, compounds 8 and 10 exhibited inhibitory effects against lipopolysaccharide-induced nitric oxide production with inhibition rates of 61 and 41%, respectively, at the concentration of 10 µM. Compounds 9 and 12 showed cytotoxic activities with cell viability varying from 29 ~ 57% at 100 µM against T98G, U87, U251, and GL261 glioma cancer cell lines. These data provide new insights on the pharmacologically active compounds of this plant widely used in folk medicine.

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