scholarly journals Discovery of benzothiazolylquinoline conjugates as novel human A 3 receptor antagonists: biological evaluations and molecular docking studies

2018 ◽  
Vol 5 (2) ◽  
pp. 171622 ◽  
Author(s):  
Bidisha Sarkar ◽  
Santanu Maiti ◽  
Gajanan Raosaheb Jadhav ◽  
Priyankar Paira
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Radioligand Binding ◽  
Physiological Responses ◽  
Docking Studies ◽  
Receptor Subtypes ◽  
Binding Data ◽  
Major Interest

Adenosine is known as an endogenous purine nucleoside and it modulates a wide variety of physiological responses by interacting with adenosine receptors. Among the four adenosine receptor subtypes, the A 3 receptor is of major interest in this study as it is overexpressed in some cancer cell lines. Herein, we have highlighted the strategy of designing the h A 3 receptor targeted novel benzothiazolylquinoline scaffolds. The radioligand binding data of the reported compounds are rationalized with the molecular docking results. Compound 6a showed best potency and selectivity at h A 3 among other adenosine receptors.

scholarly journals Adenosine Receptor Ligands: Coumarin–Chalcone Hybrids as Modulating Agents on the Activity of hARs

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4306
Author(s):  
Saleta Vazquez-Rodriguez ◽  
Santiago Vilar ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz ◽  
Eugenio Uriarte ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Radioligand Binding ◽  
Binding Pocket ◽  
Docking Studies ◽  
Receptor Ligands ◽  
Ligand Selectivity ◽  
Selective Ligands ◽  
Adenosine Receptor Ligands ◽  
Homology Models

Adenosine receptors (ARs) play an important role in neurological and psychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy and schizophrenia. The different subtypes of ARs and the knowledge on their densities and status are important for understanding the mechanisms underlying the pathogenesis of diseases and for developing new therapeutics. Looking for new scaffolds for selective AR ligands, coumarin–chalcone hybrids were synthesized (compounds 1–8) and screened in radioligand binding (hA1, hA2A and hA3) and adenylyl cyclase (hA2B) assays in order to evaluate their affinity for the four human AR subtypes (hARs). Coumarin–chalcone hybrid has been established as a new scaffold suitable for the development of potent and selective ligands for hA1 or hA3 subtypes. In general, hydroxy-substituted hybrids showed some affinity for the hA1, while the methoxy counterparts were selective for the hA3. The most potent hA1 ligand was compound 7 (Ki = 17.7 µM), whereas compound 4 was the most potent ligand for hA3 (Ki = 2.49 µM). In addition, docking studies with hA1 and hA3 homology models were established to analyze the structure–function relationships. Results showed that the different residues located on the protein binding pocket could play an important role in ligand selectivity.

Synthesis, Antiproliferative Activity and Molecular Docking of New Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives

2020 ◽  
Vol 17 (12) ◽  
pp. 951-958
Author(s):  
Pallava Nagaraju ◽  
Pedavenkatagari Narayana Reddy ◽  
Pannala Padmaja ◽  
Vinod G. Ugale
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Aromatic Aldehydes ◽  
Human Colon ◽  
Docking Studies ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Embryonic Kidney Cells ◽  
Heterocyclic Molecules

A new class of 4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and 5H,6Hpyrano[ 2,3-d]thiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized via the one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one to various aromatic aldehydes and malononitrile. This domino transformation involves the formation of pyranopyrimidine ring by the formation of three C–C bonds and one C– O bond a single synthetic operation. As the products precipitate out of the reaction, simple filtration is enough to gather the products, and thus, there is no need for work-up or column-chromatography. The synthesized thiazole/benzothiazole fused pyranopyrimidine derivatives were evaluated for their antiproliferative activity against four cancer cell lines namely DU 145 (prostate cancer), Hela (Human cervical cancer), MDA-MB-231 (breast cancer), HT-29 (Human colon cancer) and normal cell line HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal cells. Among these compounds, 2-amino-9- methoxy-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidine- 3-carbonitrile 4i exhibited the most potent antiproliferative activity against the tested cell lines. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

scholarly journals Synthesis, cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

RSC Advances ◽  
2021 ◽  
Vol 11 (50) ◽  
pp. 31433-31447
Author(s):  
Nopawit Khamto ◽  
Lada Chaichuang ◽  
Puracheth Rithchumpon ◽  
Worrapong Phupong ◽  
Phuangthip Bhoopong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Biological Potency

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.

scholarly journals Tel-Cu-NPs Catalyst: Synthesis of Naphtho[2,3-g]phthalazine Derivatives as Potential Inhibiters of Tyrosinase Enzymes and Their Investigation in Kinetic, Molecular Docking, and Cytotoxicity Studies

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1442
Author(s):  
Keerthana Selvaraj ◽  
Ali Daoud ◽  
Saud Alarifi ◽  
Akbar Idhayadhulla
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Kojic Acid ◽  
Docking Studies ◽  
Kinetic Behavior ◽  
One Pot ◽  
Catalyst Synthesis ◽  
Cytotoxicity Activity ◽  
Cytotoxicity Studies ◽  
High Yields

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized compounds, along with analysis of kinetic behavior and molecular docking studies. The synthesized compound, 1c was (IC50 = 11.5 µM) more active than kojic acid (IC50 = 78.0 µM). Lineweaver Burk plots were used to analyze the kinetic behavior of the most active compound 1c, it was reversible and competitive behavior. Compound 1c and kojic acid occurred in the presence of 2-hydroxyketone, which has the same inhibitory mechanism. The molecular docking of compound 1c and the control kojic acid were docked against 2Y9X protein via the Schrodinger Suite. The compound 1c showed a respectable dock score (−5.6 kcal/mol) compared to kojic acid with a dock score of (−5.2 kcal/mol) in the 2Y9X protein. Cytotoxicity activity was also evaluated by using HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines, and high activity for 1c (GI50 = 0.01, 0.03, and 0.04 µM, respectively) against all cell lines was found compared to standard and other compounds. Therefore, this study succeeded in testing a few promising molecules as potential antityrosinase agents.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1789 ◽  
Author(s):  
Julia Krzywik ◽  
Witold Mozga ◽  
Maral Aminpour ◽  
Jan Janczak ◽  
Ewa Maj ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Binding Modes ◽  
Colchicine Binding Site ◽  
3T3 Cell Lines ◽  
Colchicine Derivatives

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

scholarly journals Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy

2019 ◽  
Vol 20 (21) ◽  
pp. 5475 ◽  
Author(s):  
Nina Wolska ◽  
Marcin Rozalski
Keyword(s):  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Purinergic Receptor ◽  
Blood Platelets ◽  
Blood Platelet ◽  
Intracellular Camp ◽  
Receptor Subtypes ◽  
Adenosine Receptor Agonists ◽  
Anti Platelet Therapy ◽  
G Protein Coupled

Adenosine receptors are a subfamily of highly-conserved G-protein coupled receptors. They are found in the membranes of various human cells and play many physiological functions. Blood platelets express two (A2A and A2B) of the four known adenosine receptor subtypes (A1, A2A, A2B, and A3). Agonization of these receptors results in an enhanced intracellular cAMP and the inhibition of platelet activation and aggregation. Therefore, adenosine receptors A2A and A2B could be targets for anti-platelet therapy, especially under circumstances when classic therapy based on antagonizing the purinergic receptor P2Y12 is insufficient or problematic. Apart from adenosine, there is a group of synthetic, selective, longer-lasting agonists of A2A and A2B receptors reported in the literature. This group includes agonists with good selectivity for A2A or A2B receptors, as well as non-selective compounds that activate more than one type of adenosine receptor. Chemically, most A2A and A2B adenosine receptor agonists are adenosine analogues, with either adenine or ribose substituted by single or multiple foreign substituents. However, a group of non-adenosine derivative agonists has also been described. This review aims to systematically describe known agonists of A2A and A2B receptors and review the available literature data on their effects on platelet function.

scholarly journals Adenosine Receptors as Targets for Therapeutic Intervention

2014 ◽  
Vol 11 (1) ◽  
pp. 96-101 ◽  
Author(s):  
B Suvarna
Keyword(s):  
Medical Journal ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Receptor Subtypes ◽  
Therapeutic Application ◽  
Chemistry Research ◽  
Wide Range ◽  
The World ◽  
Selective Agonists ◽  
Receptor Modulators

Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer. DOI: http://dx.doi.org/10.3126/kumj.v11i1.11054 Kathmandu University Medical Journal Vol.11(1) 2013: 96-101

scholarly journals Regulation of Adenosine Receptor Subtypes during Cultivation of Human Monocytes: Role of Receptors in Preventing Lipopolysaccharide-Triggered Respiratory Burst

2004 ◽  
Vol 72 (3) ◽  
pp. 1349-1357 ◽  
Author(s):  
Andrea Thiele ◽  
Romy Kronstein ◽  
Anne Wetzel ◽  
Anja Gerth ◽  
Karen Nieber ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Receptor Agonist ◽  
Inhibitory Action ◽  
Suppressive Effect ◽  
Receptor Subtypes ◽  
Human Monocytes ◽  
Oxygen Intermediates ◽  
Adenosine Concentration

ABSTRACT Adenosine is a potent anti-inflammatory agent that modulates the function of cells involved in the inflammatory response. Here we show that it inhibits lipopolysaccharide (LPS)-induced formation of reactive oxygen intermediates (ROI) in both freshly isolated and cultured human monocytes. Blocking of adenosine uptake and inactivation of the adenosine-degrading enzyme adenosine deaminase enhanced the inhibitory action of adenosine, indicating that both pathways regulate the extracellular adenosine concentration. Adenosine-mediated inhibition could be reversed by XAC (xanthine amine congener), an antagonist of the adenosine receptor A2A, and MRS 1220 {N-9-chloro-2-(2-furanyl)[1, 2, 4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide}, an A3 receptor antagonist, in both cell populations, while DPCPX (1,3-dipropyl-8-cyclopentylxanthine), an A1 receptor antagonist, had no effect. Similar to what was seen with adenosine, CGS 21680, an A2A and A3 receptor agonist, and IB-MECA, a nonselective A1 and A3 receptor agonist, dose dependently prevented ROI formation, indicating the involvement of A3 and probably also A2A in the suppressive effect of adenosine. Pretreatment of monocytes with adenosine did not lead to changes in the LPS-induced increase in intracellular calcium levels ([Ca2+]i). Thus, participation of [Ca2+]i in the action of adenosine seems unlikely. The adenosine-mediated suppression of ROI production was found to be more pronounced when monocytes were cultured for 18 h, a time point at which changes in the mRNA expression of adenosine receptors were observed. Most prominent was the increase in the A2A receptor mRNA. These data demonstrate that cultivation of monocytes is accompanied by changes in the inhibitory action of adenosine mediated by A3 and probably also the A2A receptor and that regulation of adenosine receptors is an integral part of the monocyte differentiation program.

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