Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as Immunosuppressants

2020 ◽  
Vol 16 (4) ◽  
pp. 544-554
Author(s):  
Richa Minhas ◽  
Gulshan Bansal ◽  
Yogita Bansal
Keyword(s):  
Antioxidant Activities ◽  
Organ Transplant ◽  
Docking Studies ◽  
In Vitro Models ◽  
Autoimmune Disorders ◽  
Docking Score ◽  
Nbt Reduction ◽  
Inos Inhibition ◽  
And Control

Introduction: Nitric oxide (NO) is an important mediator in the pathogenesis and control of immune system-related disorders and its levels are modulated by inducible NO synthase (iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders. The present study aims at the development of coupled molecules via selection of pharmacophores for both immunomodulatory and antioxidant activities through iNOS inhibition. Methods: Variedly substituted coumarin moieties are coupled with naturally occurring phenols through an amide linkage and were predicted for activities using computer-based program PASS. The compounds predicted to have dual activities were synthesized. Docking studies were carried out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory and antioxidant activities. Results: The synthesized compounds were found to be pure and were obtained in good yields. Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of NBT dye and showed maximum % iNOS inhibition. In DPPH assay, compound YR4e was observed as the most potent antioxidant (EC50 0.33 µM/mL). Based on these studies, compounds YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and lower HAT value of 3.5. Conclusion: Compound YR2e can be utilized as a pharmacological agent in the prevention or treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis, organ transplant and other autoimmune disorders.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Triazolopyrimidinium salts: discovery of a new class of agents for cancer therapy

2020 ◽  
Vol 12 (5) ◽  
pp. 387-402
Author(s):  
Mariateresa Badolato ◽  
Fabrizio Manetti ◽  
Antonio Garofalo ◽  
Francesca Aiello
Keyword(s):  
Anticancer Agents ◽  
Docking Studies ◽  
In Vitro Models ◽  
Sh2 Domain ◽  
Activity Profile ◽  
Cancer Cell Growth ◽  
New Class ◽  
Src Homology 2 ◽  
Src Homology

Aim: The [1,2,4]triazolo[1,5- a]pyrimidine core is highly privileged in medicinal chemistry due to its versatile pharmacological activity profile. Recently, the search for novel anticancer agents has focused on [1,2,4]triazolo[1,5- a]pyrimidine derivatives. Results: Our hit functionalization has led to the discovery of new [1,2,4]triazolo[1,5- a]pyrimidinium salts with potential anticancer activity. Among a small library of molecules, compound 9 significantly inhibits cancer cell growth in a panel of in vitro models. Molecular docking studies and preliminary binding assay have displayed that 9 could directly bind the Src homology 2 (SH2) domain of STAT3 protein. Conclusion: Compound 9 is a novel promising lead compound that motivates additional evaluation of [1,2,4]triazolo[1,5- a]pyrimidinium salts as novel potential chemotherapeutics.

scholarly journals Antioxidant potential of some Sudanese medicinal plants used in traditional medicine

2015 ◽  
Vol 3 (2) ◽  
pp. 192 ◽  
Author(s):  
Hatil EL-Kamali ◽  
Sana E. M. Hamed
Keyword(s):  
Antioxidant Activity ◽  
Medicinal Plants ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Punica Granatum ◽  
In Vitro Models ◽  
Water Extracts ◽  
Total Antioxidant ◽  
Sudanese Medicinal Plants

<p>In the present work methanolic and water extracts of 19 medicinal plants, commonly used in Sudanese folk medicines against gastrointestinal tract, infectious diseases were investigated for their antioxidant activity. Antioxidant assays were carried out by using different in vitro models such as DPPH (2, 2-diphenyl-1picrylhydrazyl) radical scavenging and Iron chelating activity. Methanolic and water extracts of <em>Punica granatum </em>showed the highest total antioxidant activity of 71±0.03 and 73±0.01 respectively. The antioxidant activities of water extracts were poor when compared to the methanol extract. The iron chelating power of methanol and aqueous extracts of <em>Commiphora myrrha</em> 58±0.01 and <em>Azadirachta indica</em> 57±0.20 respectively.</p>

scholarly journals Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Muhammad Hanif ◽  
Khurram Shoaib ◽  
Muhammad Saleem ◽  
Nasim Hasan Rama ◽  
Sumera Zaib ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Potassium Hydroxide ◽  
Antioxidant Activities ◽  
Docking Studies ◽  
Potassium Salts ◽  
Jack Bean ◽  
Molecular Docking Studies ◽  
Oxadiazole Derivatives ◽  
Urease Inhibitory

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results.

scholarly journals Antinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Camila Carolina de Menezes Patrício Santos ◽  
Mirian Stiebbe Salvadori ◽  
Vanine Gomes Mota ◽  
Luciana Muratori Costa ◽  
Antonia Amanda Cardoso de Almeida ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Thiobarbituric Acid ◽  
In Vitro Models ◽  
Control Group ◽  
Second Phase ◽  
Hot Plate Test ◽  
Antinociceptive Effects

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P<0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P<0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

Nrf2/HO-1 Mediated Antioxidant Activities, Cytotoxicity Analysis and LCESI/ MS Profiling of Eulophia nuda L.

2020 ◽  
Vol 10 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Vikas Nanekar ◽  
Varsha Shriram ◽  
Tushar Khare ◽  
Vinay Kumar
Keyword(s):  
Free Radical ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Fold Increase ◽  
In Vitro Models ◽  
Free Radical Scavenging ◽  
Related Factor ◽  
Mcf7 Cells ◽  
Esi Ms

Background: Eulophia nuda, is a highly medicinal orchid with strong antioxidant and anticancer potentials in traditional systems of medicine. But few reports are available on the scientific validation. The aim of the study was to investigate phytochemical constituents, antioxidant and cytotoxic efficacies of extracts of Eulophia nuda, and the underlying mechanisms-of-action via upregulation of nuclear transcription factor-erythroid-2 related factor (Nrf2) and hemeoxygenase-1 (HO-1) pathways. Methods: Petroleum Ether (PEE), Ethyl Acetate (EAE), Methanol (ME) and Aqueous Methanol (AqME) extracts of shade dried tubers were obtained and concentrated in vacuo. Total phenols, flavonoids, condensed tannins, ascorbic acid and carotenoids were estimated from the extracts using standard methods. Antioxidant activities of extracts were determined by total antioxidant, FRAP, ABTS, DPPH, OH, H2O2, NO, O2 ·- radical scavenging assays. Cytotoxicity of EAE and ME were assessed against MCF7 cells in vitro. LC-ESI/MS profiling of EAE was carried out. Quantitative Real-Time (qRT) PCR was used for the expression analysis of Nrf2 and HO1 genes in EAE-treated MCF7 cells. Results: In vitro models confirmed strong dose-dependent antioxidant and free-radical scavenging potencies of E. nuda tuber extracts. Overall antioxidant efficacies were in the order EAE > ME > AqME > PEE. EAE showed striking cytotoxicity followed by ME (0.86% and 5.17% cell survival at 1000 µg ml-1, respectively). LC-ESI/MS profiling of most potent extract EAE revealed 37 identified compounds including catechin, taxifolin, tocopherol, trigallic acid and chlorogenic acid, all known for their strong antioxidant/anticancer properties. Expression levels of Nrf2 and HO1 genes were up-regulated in MCF7 cells beyond 50 μg ml-1 extract concentration with > 2-fold increase at 200 µg ml-1 EAE. Conclusion: The data demonstrated that E. nuda extracts possess strong free radical scavenging and antioxidant efficacies and the mechanism of action may be via inducing Nrf2 and HO-1.

scholarly journals A Simple Aspect Ratio Dependent Method of Patterning Microwells for Selective Cell Attachment

2018 ◽  
Author(s):  
Erik A. Zavrel ◽  
Michael L. Shuler ◽  
Xiling Shen
Keyword(s):  
Cell Culture ◽  
Cell Attachment ◽  
In Vitro Models ◽  
Contact Printing ◽  
Deep Well ◽  
Biomimetic Approach ◽  
Authentic Environment ◽  
And Control

3-D culture has been shown to provide cells with a more physiologically authentic environment than traditional 2-D (planar) culture [1, 2]. 3-D cues allow cells to exhibit more realistic functions and behaviors, e.g., adhesion, spreading, migration, metabolic activity, and differentiation. Knowledge of changes in cell morphology, mechanics, and mobility in response to geometrical cues and topological stimuli is important for understanding normal and pathological cell development [3]. Microfabrication provides unique in vitro approaches to recapitulating in vivo conditions due to the ability to precisely control the cellular microenvironment [4, 5]. Microwell arrays have emerged as robust alternatives to traditional 2D cell culture substrates as they are relatively simple and compatible with existing laboratory techniques and instrumentation [6, 7]. In particular, microwells have been adopted as a biomimetic approach to modeling the unique micro-architecture of the epithelial lining of the gastrointestinal (GI) tract [8–10]. The inner (lumen-facing) surface of the intestine has a convoluted topography consisting of finger-like projections (villi) with deep well-like invaginations (crypts) between them. The dimensions of villi and crypts are on the order of hundreds of microns (100–700 μm in height and 50–250 μm in diameter) [11]. While microwells have proven important in the development of physiologically realistic in vitro models of human intestine, existing methods of ensuring their surface is suitable for cell culture are lacking. Sometimes it is desirable to selectively seed cells within microwells and confine or restrict them to the microwells in which they are seeded. Existing methods of patterning microwells for cell attachment either lack selectivity, meaning cells can adhere and migrate anywhere on the microwell array, i.e., inside microwells or outside of them, or necessitate sophisticated techniques such as micro-contact printing, which requires precise alignment and control to selectively pattern the bottoms of microwells for cell attachment [12, 13].

scholarly journals Histone Deacetylase Inhibitors and Antioxidants From the Root of Gluta usitata

2019 ◽  
Vol 14 (12) ◽  
pp. 1934578X1989537
Author(s):  
Pakit Kumboonma ◽  
Somprasong Saenglee ◽  
Thanaset Senawong ◽  
Chanokbhorn Phaosiri
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Antioxidant Activities ◽  
Hdac Inhibitors ◽  
Docking Studies ◽  
Resonance Spectroscopy ◽  
In Vitro Experiments ◽  
Magnetic Resonance Spectroscopy Data

A new glycoside, glutacoside (1), as well as 6 known compounds was isolated and identified from the root of Gluta usitata. Their structures were determined by Infrared spectroscopy, Mass spectroscopy, and 1-Dimensional and 2-dimensional nuclear magnetic resonance spectroscopy data. The histone deacetylase (HDAC) inhibitory and antioxidant activities of the obtained compounds were evaluated. Molecular docking experiments of the selected compound with representatives of class I (HDAC2 and HDAC8) and class II (HDAC4 and HDAC7) HDAC isoforms displayed potential isoform-selective HDAC inhibitors. Molecular docking data showed consistent results to the in vitro experiments with the highest potency against HDAC8. The docking studies suggested that the phenolic and carbonyl group can be favorably accommodated at the gorge region of the binding site. Furthermore, the phenolic groups also acted as major roles for antioxidant activities.

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