scholarly journals Hybridization of Curcumin Analogues with Cinnamic Acid Derivatives as Multi-Target Agents Against Alzheimer’s Disease Targets

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4958 ◽  
Author(s):  
Eirini Chainoglou ◽  
Argyris Siskos ◽  
Eleni Pontiki ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Cinnamic Acid ◽  
Hydrophobic Interactions ◽  
Docking Studies ◽  
The Novel ◽  
Chromatography Method ◽  
Cinnamic Acid Derivatives ◽  
Curcumin Analogues ◽  
Antioxidant Agents ◽  
Good Oral Bioavailability

The synthesis of the new hybrids followed a hybridization with the aid of hydroxy-benzotriazole (HOBT) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI.HCL) in dry DMF or thionyl chloride between curcumin analogues and cinnamic acid derivatives. IR, 1H-NMR, 13C-NMR, LC/MS ESI+, and elemental analysis were used for the confirmation of the structures of the novel hybrids. The lipophilicity values of compounds were calculated theoretically and experimentally via the reversed chromatography method as RM values. The novel derivatives were studied through in vitro experiments for their activity as antioxidant agents and as inhibitors of lipoxygenase, cyclooxygenase-2, and acetyl-cholinesterase. All the compounds showed satisfying anti-lipid peroxidation activity of linoleic acid induced by 2,2′-azobis(2-amidinopropane) hydrochloride (AAPH). Hybrid 3e was the most significant pleiotropic derivative, followed by 3a. According to the predicted results, all hybrids could be easily transported, diffused, and absorbed through the blood–brain barrier (BBB). They presented good oral bioavailability and very high absorption with the exception of 3h. No inhibition for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was noticed. According to the Ames test, all the hybrids induced mutagenicity with the exception of 3d. Efforts were conducted a) to correlate the in vitro results with the most important physicochemical properties of the structural components of the molecules and b) to clarify the correlation of actions among them to propose a possible mechanism of action. Docking studies were performed on soybean lipoxygenase (LOX) and showed hydrophobic interactions with amino acids. Docking studies on acetylcholinesterase (AChE) exhibited: (a) hydrophobic interactions with TRP281, LEU282, TYR332, PHE333, and TYR336 and (b) π-stacking interactions with TYR336.

scholarly journals Cinnamic Acid Derivatives and Their Biological Efficacy

2020 ◽  
Vol 21 (16) ◽  
pp. 5712 ◽  
Author(s):  
Ngonidzashe Ruwizhi ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Cinnamic Acid ◽  
Neurological Disorders ◽  
Bacterial Infections ◽  
Antimalarial Activity ◽  
Aureus Strain ◽  
Cinnamic Acid Derivatives ◽  
Biological Efficacy ◽  
Bioactive Agents ◽  
Acid Functional Group

The role played by cinnamic acid derivatives in treating cancer, bacterial infections, diabetes and neurological disorders, among many, has been reported. Cinnamic acid is obtained from cinnamon bark. Its structure is composed of a benzene ring, an alkene double bond and an acrylic acid functional group making it possible to modify the aforementioned functionalities with a variety of compounds resulting in bioactive agents with enhanced efficacy. The nature of the substituents incorporated into cinnamic acid has been found to play a huge role in either enhancing or decreasing the biological efficacy of the synthesized cinnamic acid derivatives. Some of the derivatives have been reported to be more effective when compared to the standard drugs used to treat chronic or infectious diseases in vitro, thus making them very promising therapeutic agents. Compound 20 displayed potent anti-TB activity, compound 27 exhibited significant antibacterial activity on S. aureus strain of bacteria and compounds with potent antimalarial activity are 35a, 35g, 35i, 36i, and 36b. Furthermore, compounds 43d, 44o, 55g–55p, 59e, 59g displayed potent anticancer activity and compounds 86f–h were active against both hAChE and hBuChE. This review will expound on the recent advances on cinnamic acid derivatives and their biological efficacy.

scholarly journals Germinated and Ungerminated Seeds Extract from TwoLupinusSpecies: Biological Compounds Characterization and In Vitro and In Vivo Evaluations

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Bogdan Andor ◽  
Corina Danciu ◽  
Ersilia Alexa ◽  
Istvan Zupko ◽  
Elena Hogea ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Therapeutic Potential ◽  
Lupinus Albus ◽  
Biological Evaluation ◽  
Lupinus Angustifolius ◽  
Cinnamic Acid Derivatives ◽  
Natural Agents ◽  
Germinated Seeds

In recent years, nutraceuticals attracted a great amount of attention in the biomedical research due to their significant contribution as natural agents for prevention of various health issues. Ethanolic extracts from the ungerminated and germinated seeds ofLupinus albusL. andLupinus angustifoliusL. were analyzed for the content in isoflavones (genistein) and cinnamic acid derivatives. Additionally, the extracts were evaluated for antimicrobial, antiproliferative, and anti-inflammatory properties, using in vitro and in vivo tests. Germination proved to be a method of choice in increasing the amount of genistein and cinnamic acid derivatives in bothLupinus albusL. andLupinus angustifolius L.seeds. Biological evaluation of all vegetal extracts revealed a weak therapeutic potential for both ungerminated and germinated seeds.

Antiviral Activity of Cholesteryl Esters of Cinnamic Acid Derivatives

1998 ◽  
Vol 53 (9-10) ◽  
pp. 883-887 ◽  
Author(s):  
Angel S. Galabov ◽  
Lubomira Nikolaeva ◽  
Daniela Todorova ◽  
Tsenka Milkova
Keyword(s):  
Antiviral Activity ◽  
Cinnamic Acid ◽  
Cholesteryl Esters ◽  
Cinnamic Acid Derivatives ◽  
Steryl Esters ◽  
Causative Agents ◽  
Marked Activity ◽  
Taxonomic Groups

Cholesteryl 3”,4”-dimethoxycinnamate (7) and a new synthesized o-coumaroyl ester of 3β- (2’-hydroxyethoxy)-cholest-5-en (13) exhibited a marked activity against poliovirus type 1 (Mahoney). Compound 7 showed an approximately 20-fold greater selectivity in its antiviral activity than compound 13. These compounds were selected from thirteen steryl esters of cinnamic acid derivatives through an in vitro antiviral screening against viruses belonging to taxonomic groups with causative agents of important human infectious diseases to which chemotherapy is indicated, i.e. Picornaviridae, Orthomyxoviridae, Paramyxoviridae and Herpesviridae.

Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as Sm HDAC8 Inhibitors for the Treatment of Schistosomiasis

ChemMedChem ◽  
2018 ◽  
Vol 13 (15) ◽  
pp. 1517-1529 ◽  
Author(s):  
Theresa Bayer ◽  
Alokta Chakrabarti ◽  
Julien Lancelot ◽  
Tajith B. Shaik ◽  
Kristin Hausmann ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Cinnamic Acid Derivatives ◽  
In Vitro Characterization ◽  
Hdac8 Inhibitors

scholarly journals Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4941
Author(s):  
Ivana I. Jevtić ◽  
Thu Hang Lai ◽  
Jelena Z. Penjišević ◽  
Sladjana Dukić-Stefanović ◽  
Deana B. Andrić ◽  
...  
Keyword(s):  
Binding Assay ◽  
Docking Studies ◽  
Emission Tomography ◽  
Binding Affinities ◽  
The Novel ◽  
Competitive Binding Assay ◽  
Mao B ◽  
Positron Emission ◽  
Further Development

Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.

Novel Cinnamic Acid Derivatives as Potential PPARδ Agonists for Metabolic Syndrome: Design, Synthesis, Evaluation and Docking Studies

2020 ◽  
Vol 17 (3) ◽  
pp. 338-347
Author(s):  
Ajay Chauhan ◽  
Ajmer S. Grewal ◽  
Deepti Pandita ◽  
Viney Lather
Keyword(s):  
Cinnamic Acid ◽  
In Silico ◽  
Metabolic Disorders ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Cinnamic Acid Derivatives ◽  
In Silico Docking ◽  
Study Results

Background: Peroxisome proliferator-activated receptor (PPAR) δ is expressed universally in the entire tissues, particularly in those concerned with the lipid metabolism. PPAR δ stimulation alters body’s energy fuel preference to fat from glucose and shows up as an emerging pharmacological target for the treatment of metabolic disorders. Methods: A new series of cinnamic acid derivatives was synthesized and evaluated for the antidiabetic and antiinflammatory activities in the animal models followed by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPARδ protein. Results: Amongst the synthesized molecules, compound 3 showed higher antidiabetic activity in oral glucose tolerance test and compound 1 showed higher antiinflammatory activity in the carrageenan induced rat paw oedema method. The in vivo study results were supported by the similar in silico molecular docking results. Most of the synthesized derivatives showed drug likeness as depicted via Lipinski’s rule of 5. Conclusion: These molecules can serve as the early hit molecules for the discovery of safe, effective and bioavailable PPARδ agonists for the potential treatment of various metabolic disorders.</P>

scholarly journals New sulfonamide hybrids: synthesis, in vitro antimicrobial activity and docking study of some novel sulfonamide derivatives bearing carbamate/acyl-thiourea scaffolds

2018 ◽  
Vol 7 (5) ◽  
pp. 370-385 ◽  
Author(s):  
Modather F Hussein
Keyword(s):  
Quantum Chemical ◽  
Density Functional ◽  
Docking Study ◽  
Docking Studies ◽  
Ethyl Carbamate ◽  
The Novel ◽  
Microbial Activities ◽  
Ligand Efficiency ◽  
Functional Theory

In this study, the novel hybrids sulfonamide carbamates were synthesized by treatment of N-substituted 4-isothiocyanatophenyl sulfonamides with ethyl carbamate in dry 1,4-dioxane at reflux temperature in the presence of triethylamine. Also, treatment of Phenylacetylisothiocyanate with sulfanilamide in refluxing acetonitrile afforded the corresponding hybrid sulfonamide acylthiourea derivatives. The anti-microbial activities of the synthesized compounds were evaluated. Ethyl ({4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl)-phenyl]carbamothioyl)- carbamate and 2-Phenyl-N-((4-(N-thiazol-2-yl)sulfamoyl)-phenyl)carbamothioyl)-acetamide exhibited the best activity against tested bacteria. Molecular docking studies for the final compounds were performed using the Open Eye docking suite. Moreover, Ligand efficiency (LE) and lipophilic ligand efficiency (LLE) parameters for Ethyl ({4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl)phenyl]carbamothioyl)-carbamate and 2-Phenyl-N-((4-(N-thiazol-2- yl)sulfamoyl)phenyl)carb-amothioyl)acetamide were evaluated. Quantum chemical calculations based on density functional theory (DFT) have been performed.

scholarly journals Front Cover: Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as Sm HDAC8 Inhibitors for the Treatment of Schistosomiasis (ChemMedChem 15/2018)

ChemMedChem ◽  
2018 ◽  
Vol 13 (15) ◽  
pp. 1488-1488
Author(s):  
Theresa Bayer ◽  
Alokta Chakrabarti ◽  
Julien Lancelot ◽  
Tajith B. Shaik ◽  
Kristin Hausmann ◽  
...  
Keyword(s):  
Cinnamic Acid ◽  
Cinnamic Acid Derivatives ◽  
Front Cover ◽  
In Vitro Characterization ◽  
Hdac8 Inhibitors

scholarly journals Identification of Chalcone Derivatives as Inhibitors of Leishmania infantum Arginase and Promising Antileishmanial Agents

2021 ◽  
Vol 8 ◽  
Author(s):  
Andreza R. Garcia ◽  
Danielle M. P. Oliveira ◽  
Jessica B. Jesus ◽  
Alessandra M. T. Souza ◽  
Ana Carolina R. Sodero ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Hydrophobic Interactions ◽  
Docking Studies ◽  
Host Cells ◽  
Polyamine Biosynthesis ◽  
Reference Drug ◽  
Growth And Survival ◽  
Chalcone Derivatives ◽  
Antileishmanial Drug

Arginase catalyzes the hydrolysis of l-arginine into l-ornithine and urea, acting as a key enzyme in the biosynthesis of polyamines. Leishmania growth and survival is dependent on polyamine biosynthesis; therefore, inhibition of Leishmania arginase may be a promising therapeutic strategy. Here, we evaluated a series of thirty-six chalcone derivatives as potential inhibitors of Leishmania infantum arginase (LiARG). In addition, the activity of selected inhibitors against L. infantum parasites was assessed in vitro. Seven compounds exhibited LiARG inhibition above 50% at 100 μM. Among them, compounds LC41, LC39, and LC32 displayed the greatest inhibition values (72.3 ± 0.3%, 71.9 ± 11.6%, and 69.5 ± 7.9%, respectively). Molecular docking studies predicted hydrogen bonds and hydrophobic interactions between the most active chalcones (LC32, LC39, and LC41) and specific residues from LiARG's active site, such as His140, Asn153, His155, and Ala193. Compound LC32 showed the highest activity against L. infantum promastigotes (IC50 of 74.1 ± 10.0 μM), whereas compounds LC39 and LC41 displayed the best results against intracellular amastigotes (IC50 of 55.2 ± 3.8 and 70.4 ± 9.6 μM, respectively). Moreover, compound LC39 showed more selectivity against parasites than host cells (macrophages), with a selectivity index (SI) of 107.1, even greater than that of the reference drug Fungizone®. Computational pharmacokinetic and toxicological evaluations showed high oral bioavailability and low toxicity for the most active compounds. The results presented here support the use of substituted chalcone skeletons as promising LiARG inhibitors and antileishmanial drug candidates.

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