A strategic approach to the synthesis of functionalized spirooxindole pyrrolidine derivatives: in vitro antibacterial, antifungal, antimalarial and antitubercular studies

2015 ◽  
Vol 39 (1) ◽  
pp. 520-528 ◽  
Author(s):  
Saoussen Haddad ◽  
Sarra Boudriga ◽  
Tarunkumar Nanjibhai Akhaja ◽  
Jignesh Priyakant Raval ◽  
François Porzio ◽  
...  
Keyword(s):  
Dft Calculations ◽  
Biological Activities ◽  
Cycloaddition Reaction ◽  
Strategic Approach

A series of spirooxindole pyrrolidine derivatives has been synthesized and evaluated for theirin vitrobiological activities. The observed regio- and stereoselectivity of the cycloaddition reaction has been rationalized using DFT calculations.

Synthesis of novel dispiropyrrolothiazoles by three-component 1,3-dipolar cycloaddition and evaluation of their antimycobacterial activity

RSC Advances ◽  
2014 ◽  
Vol 4 (103) ◽  
pp. 59462-59471 ◽  
Author(s):  
Saoussen Haddad ◽  
Sarra Boudriga ◽  
François Porzio ◽  
Armand Soldera ◽  
Moheddine Askri ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dft Calculations ◽  
Cycloaddition Reaction ◽  
Antimycobacterial Activity ◽  
Dipolar Cycloaddition

A series of dispiropyrrolothiazoles derivatives has been synthesized screenedin vitroagainstMycobacterium tuberculosisH37Rv. The observed regio- and stereoselectivity of the cycloaddition reaction has been rationalized by DFT calculations.

Pharmacological and Cellular Significance of Triazole-Surrogated Compounds

2020 ◽  
Vol 23 (23) ◽  
pp. 2305-2572
Author(s):  
Naimish Kumar Verma ◽  
Dhananjoy Mondal ◽  
Smritilekha Bera
Keyword(s):  
Biological Activities ◽  
Cycloaddition Reaction ◽  
Antidepressant Drugs ◽  
Triazole Ring ◽  
Building Blocks ◽  
Base Hydrolysis ◽  
Covalent Attachment ◽  
In Vivo Studies

: Heterocyclic compounds have been at the hierarchy position in academia, and industrial arena, particularly the compounds containing triazole-core are found to be potent with a broad range of biological activities. The resistance of triazole ring towards chemical (acid and base) hydrolysis, oxidative and reductive reaction conditions, metabolic degradation and its higher aromatic stabilization energy makes it a better heterocyclic core as therapeutic agents. These triazole-linked compounds are used for clinical purposes for antifungal, anti-mycobacterium, anticancer, anti-migraine and antidepressant drugs. Triazole scaffolds are also found to act as a spacer for the sake of covalent attachment of the high molecular weight bio-macromolecules with an experimental building blocks to explore structure-function relationships. Herein, several methods and strategies for the synthesis of compounds with 1,2,3-triazole moiety exploring Hüisgen, Meldal and Sharpless 1,3-dipolar cycloaddition reaction between azide and alkyne derivatives have been deliberated for a series of representative compounds. Moreover, this review article highlights in-depth applications of the [3+2]-cycloaddition reaction for the advances of triazole-containing antibacterial as well as metabolic labelling agents for the in vitro and in vivo studies on cellular level.

Dwindling status of Epimedium Elatum (Morren & Decne) and its geographical distribution in Kashmir Himalaya, India

2018 ◽  
pp. 47-52
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Conservation Status ◽  
Natural Populations ◽  
Culture Techniques ◽  
Kashmir Himalayas ◽  
Near Future ◽  
First Time ◽  
Tissue Culture Techniques

Epimedium elatum (Morren & Decne) of family Berberidaceace is a rare perennial medicinal plant, endemic to high altitude forests of Northwestern Himalayas in India. Ethnobotanically, it has been used as an ingredient for treatment of bone-joint disorders, impotence and kidney disorders in Kashmir Himalayas. Phytochemically, it is rich in Epimedin ABC and Icariin; all of these have been demonstrated to possess remarkable biological activities like PDE-5 inhibition (treatment of erectile dysfunction), anticancer, antiosteoporosis antioxidant and antiviral properties. The present investigation reports its traditional usage, comprehensive distribution and conservation status from twenty ecogeographical regions in Kashmir Himalayas, India. The species was reported from Gurez valley for the first time. Numerous threats like excessive grazing, deforestration, habitat fragmentation, tourism encroachment, landslides and excessive exploitation have decreased its natural populations in most of the surveyed habitats. Consequently, its existence may become threatened in near future if timely conservation steps are not taken immediately by concerned stakeholders involved in medicinal plant research. Moreover, use of plant tissue culture techniques is recommended for development of its in vitro propagation protocols. Therefore, introduction of this medicinal plant in botanical gardens, protected sites and development of monitoring programmes are needed for its immediate conservation in Northwestern Himalayas, India.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

2020 ◽  
Vol 27 ◽  
Author(s):  
Leydianne Leite de Siqueira Patriota ◽  
Dayane Kelly Dias do Nascimento Santos ◽  
Bárbara Rafaela da Silva Barros ◽  
Lethícia Maria de Souza Aguiar ◽  
Yasmym Araújo Silva ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Trypsin Inhibitor ◽  
Hemolytic Activity ◽  
Moringa Oleifera ◽  
Biological Activities ◽  
Hematological Parameters ◽  
Behavioral Alterations ◽  
Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Comparative Analysis of In-Vitro Biological Activities of Methyl Eugenol Rich Cymbopogon khasianus Hack., Leaf Essential Oil with Pure Methyl Eugenol Compound

2020 ◽  
Vol 21 (10) ◽  
pp. 927-938 ◽  
Author(s):  
Roktim Gogoi ◽  
Rikraj Loying ◽  
Neelav Sarma ◽  
Twahira Begum ◽  
Sudin K. Pandey ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Essential Oil ◽  
Biological Activities ◽  
Methyl Eugenol ◽  
Dpph Assay ◽  
Pure Compound ◽  
Allium Cepa Assay ◽  
Anti Inflammatory ◽  
Lemongrass Essential Oil

Background: The essential oil of methyl eugenol rich Cymbopogon khasianus Hack. was evaluated and its bioactivities were compared with pure methyl eugenol. So far, methyl eugenol rich essential oil of lemongrass was not studied for any biological activities; hence, the present study was conducted. Objective: This study examined the chemical composition of essential oil of methyl eugenol rich Cymbopogon khasianus Hack., and evaluated its antioxidant, anti-inflammatory, antimicrobial, and herbicidal properties and genotoxicity, which were compared with pure compound, methyl eugenol. Material and Methods: Methyl eugenol rich variety of Cymbopogon khasianus Hack., with registration no. INGR18037 (c.v. Jor Lab L-9) was collected from experimental farm CSIR-NEIST, Jorhat, Assam (26.7378°N, 94.1570°E). The essential oil wasobtained by hydro-distillation using a Clevenger apparatus. The chemical composition of the essential oil was evaluated using GC/MS analysis and its antioxidant (DPPH assay, reducing power assay), anti-inflammatory (Egg albumin denaturation assay), and antimicrobial (Disc diffusion assay, MIC) properties, seed germination effect and genotoxicity (Allium cepa assay) were studied and compared with pure Methyl Eugenol compound (ME). Results: Major components detected in the Essential Oil (EO) through Gas chromatography/mass spectroscopy analysis were methyl eugenol (73.17%) and β-myrcene (8.58%). A total of 35components were detected with a total identified area percentage of 98.34%. DPPH assay revealed considerable antioxidant activity of methyl eugenol rich lemongrass essential oil (IC50= 2.263 μg/mL), which is lower than standard ascorbic acid (IC50 2.58 μg/mL), and higher than standard Methyl Eugenol (ME) (IC50 2.253 μg/mL). Methyl eugenol rich lemongrass EO showed IC50 38.00 μg/mL, ME 36.44 μg/mL, and sodium diclofenac 22.76 μg/mL, in in-vitro anti-inflammatory test. Moderate antimicrobial activity towards the 8 tested microbes was shown by methyl eugenol rich lemongrass essential oil whose effectiveness against the microbes was less as compared to pure ME standard. Seed germination assay further revealed the herbicidal properties of methyl eugenol rich essential oil. Moreover, Allium cepa assay revealed moderate genotoxicity of the essential oil. Conclusion: This paper compared the antioxidant, anti-inflammatory, antimicrobial, genotoxicity and herbicidal activities of methyl eugenol rich lemongrass with pure methyl eugenol. This methyl eugenol rich lemongrass variety can be used as an alternative of methyl eugenol pure compound. Hence, the essential oil of this variety has the potential of developing cost-effective, easily available antioxidative/ antimicrobial drugs but its use should be under the safety range of methyl eugenol and needs further clinical trials.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

Novel Iodinated Hydrazide-hydrazones and their Analogues as Acetyl- and Butyrylcholinesterase Inhibitors

2020 ◽  
Vol 20 (23) ◽  
pp. 2106-2117
Author(s):  
Martin Krátký ◽  
Šárka Štěpánková ◽  
Michaela Brablíková ◽  
Katarína Svrčková ◽  
Markéta Švarcová ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Parameters ◽  
Covalent Binding ◽  
Docking Studies ◽  
Potent Inhibition ◽  
Brain Barrier Permeability ◽  
Electric Eel ◽  
Ic50 Values ◽  
Ellman’S Method

Background: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias’ treatment. Objective: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. Methods: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman’s method. We calculated also physicochemical and structural parameters for CNS delivery. Results: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. Conclusion: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

2018 ◽  
Vol 15 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Parvesh Singh ◽  
Nomandla Ngcoya ◽  
Ramgopal Mopuri ◽  
Nagaraju Kerru ◽  
Neha Manhas ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Catalytic Site ◽  
Docking Simulations ◽  
In Silico Docking ◽  
Anti Oxidant

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

1'-methylspiro[indoline-3,4'-piperidine] Derivatives: Design, Synthesis, Molecular Docking and Anti-tumor Activity Studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Junjian Li ◽  
Lianbao Ye ◽  
Yuanyuan Wang ◽  
Ying Liu ◽  
Xiaobao Jin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Active Sites ◽  
Biological Activities ◽  
Significant Inhibition ◽  
Alkaline Condition ◽  
Discovery Studio ◽  
Hela Cell Lines ◽  
Antiproliferative Activities

Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological activities and some drug molecules in many aspects. In recent years, it has attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio 2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target proteins from PDB database. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, - 38.3292 kcal/mol, -33.3653 kcal/mol respectively. Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A- 549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites which encourage us to conduct further evaluation such as the kinase experiment.

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