scholarly journals Hybrids of Thiazolidin-4-Ones and 1,3,4-Thiadiazole: Synthesis and Biological Screening of A Potential New Class of Acetylcholinesterae Inhibitors

2021 ◽  
Vol 12 (3) ◽  
pp. 2800-2812
Keyword(s):  
Enzyme Inhibitors ◽  
Future Research ◽  
Propanoic Acid ◽  
Standard Drug ◽  
Spectral Techniques ◽  
New Class ◽  
Ache Inhibitors ◽  
Thiadiazole Derivative ◽  
Ellman’S Method

Using propanoic acid and thiosemicarbazide as starting materials, a new sequence of thiazolidin-4-one analogs with thiadiazole derivative was synthesized in appreciable yield. Spectral techniques such as IR, 1H NMR, 13C NMR, and MS were used to validate the structures of the synthesized compounds (4a-t). In vitro acetylcholinesterase inhibitory activity of these synthesized compounds was assessed using an Ellman's method spectrophotometer and donepezil as a standard drug. Compounds 2-((5-ethyl-1,3,4-thiadiazol-2-yl)imino)-5-(4-methylbenzylidene)thiazolidin-4-one(4o) and 5-(4-(benzyloxy)benzylidene)-2-((5-ethyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one(4i) were found to be potent AChE enzyme inhibitors, with pIC50 (mM) values of 1.30±0.007 and 1.22±0.002, respectively. Finally, these significant results could pave the way for the development of new AChE inhibitors and will serve as the basis for future research.

scholarly journals Kinetics of acetylcholinesterase inhibition by an aqueous extract of Cuminum cyminum seeds.

2014 ◽  
Vol 2 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Suresh Kumar ◽  
Suman Chowdhury
Keyword(s):  
Aqueous Extract ◽  
Side Effect ◽  
Competitive Inhibition ◽  
Kinetic Studies ◽  
Symptomatic Treatment ◽  
Acetylcholinesterase Inhibition ◽  
Ache Inhibitors ◽  
Maximum Inhibition ◽  
Ellman’S Method

The cholinergic hypothesis of Alzheimer’s disease (AD) has provided the rationale for the current pharmacotherapy of this disease. Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy for the symptomatic treatment of AD. The current drugs available in the market has shown various side effect which prompted scientist to search for new and potent AChE inhibitors which exerts minimal side effect in AD patient. In present study, an aqueous extract of Cumin cyminum was tested for in vitro acetylcholinesterase inhibitory activity based on Ellman’s method. C. cyminum showed maximum inhibition of 76.90±0.003% in an aqueous extract at 50μg/ml final concentration. Further studies were conducted to elucidate the mode of AChE inhibition by kinetic studies. Competitive inhibition was observed at lower concentrations (12.5μg/ml & 25μg/ml) and mixed inhibition was observed at higher concentrations (50μg/ml & 100μg/ml). DOI: http://dx.doi.org/10.3126/ijasbt.v2i1.9348   Int J Appl Sci Biotechnol, Vol 2(1): 64-68

scholarly journals Chemical Composition and Cytotoxic Activity of the Essential Oil and Oleoresins of In Vitro Micropropagated Ansellia africana Lindl: A Vulnerable Medicinal Orchid of Africa

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4556
Author(s):  
Md. Moshfekus Saleh-E-In ◽  
Paromik Bhattacharyya ◽  
Johannes Van Staden
Keyword(s):  
Essential Oil ◽  
Cytotoxic Activity ◽  
Butyl Acetate ◽  
Herbal Medicines ◽  
Future Research ◽  
Naphthalene Acetic Acid ◽  
Ms Medium ◽  
Indole Butyric Acid ◽  
Standard Drug

Orchids are rich treasure troves of various important phytomolecules. Among the various medicinal orchids, Ansellia africana stands out prominently in the preparing of various herbal medicines due to its high therapeutic importance. The nodal explants of A. africana were sampled from asymbiotically germinated seedlings on basal Murashige and Skoog (MS) medium and were micropropagated in MS medium supplemented with 3% sucrose and 10 µM meta topolin (mT) + 5 µM naphthalene acetic acid (NAA) +15 µM indole butyric acid (IBA) + 30 µM phloroglucinol (PG). In the present study, the essential oil was extracted by hydrodistillation and the oleoresins by the solvent extraction method from the micropropagated A. africana. The essential oil and the oleoresins were analysed by Gas Chromatography (GC) and GC/MS (Mass spectrometry). A total of 84 compounds were identified. The most predominant components among them were linoleic acid (18.42%), l-ascorbyl 2,6-dipalmitate (11.50%), linolenic acid (10.98%) and p-cresol (9.99%) in the essential oil; and eicosane (26.34%), n-butyl acetate (21.13%), heptadecane (16.48%) and 2-pentanone, 4-hydroxy-4-methyl (11.13%) were detected in the acetone extract; heptadecane (9.40%), heneicosane (9.45%), eicosane (6.40%), n-butyl acetate (14.34%) and styrene (22.20%) were identified and quantified in the ethyl acetate extract. The cytotoxic activity of essential oil and oleoresins of micropropagated A. africana was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) assay on Vero cells compared to the standard drug doxorubicin chloride. The present research contains primary information about the therapeutic utility of the essential oil and oleoresins of A. africana with a promising future research potential of qualitative and quantitative improvement through synchronised use of biotechnological techniques.

scholarly journals S-Methylene linkage comprising 1,3,4-oxadiazoles: synthesis, reaction optimization and in vitro anti-microbial potential

2021 ◽  
pp. 109-118
Author(s):  
Gautam M. Dhuda ◽  
Khushal M. Kapadiya ◽  
Paresh D. Ladwa ◽  
Jayesh J. Modha
Keyword(s):  
Biological Evaluation ◽  
Synthesis Reaction ◽  
Bacterial Strains ◽  
Standard Drug ◽  
New Class ◽  
Microdilution Method ◽  
Reaction Optimization ◽  
Broth Microdilution Method ◽  
Microbial Potential

To generate a new class of scaffolds with amended anti-microbial potency, synthesis and in vitro biological evaluation of a series of 2-((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)methylthio)-5-substitutedphenyl-1,3,4-oxadiazole (5a-5o) having S-Methylene linkage between the two 1,3,4-diisoxazole rings is reported. Anti-microbial properties of the entire compounds were investigated in a broad panel of some selected gram-positive bacterial strains, gram-negative bacterial strain, and fungal strains using the broth microdilution method. The results were dominant on –Cl and –NO2 functionality than the used standard drug.

Anodyne activities of New Tetrazole derivatives from Triazine

2020 ◽  
Vol 11 (3) ◽  
pp. 3377-3383
Author(s):  
Arulmozhi R ◽  
Abirami N ◽  
Helen P Kavitha ◽  
Arulmurugan S ◽  
Vinoth Kumar J
Keyword(s):  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Pharmaceutical Chemistry ◽  
Tail Flick ◽  
Structural Fragment ◽  
Hot Plate ◽  
Standard Drug ◽  
New Class ◽  
Novel Drugs ◽  
Tetrazole Derivatives

The creation of novel drugs containing a tetrazole ring as a structural fragment has contributed considerably to the outstanding achievements of the pharmaceutical chemistry in the last decade. Tetrazoles are the heterocyclic compounds having diverse biological activities such as analgesic, antiinflammation, antimicrobial, anticancer, antidiabetic, etc., and an impending source in biosciences. In this paper, the authors describe the synthesis of novel tetrazoles from N, N-( 6-Phenyl-1,3,5-triazine-2,4-diyl) dibenzamide (PTDDB) and 2-phenyl-4, 6-di(2H-tetrazole-2-yl)-1,3,5-triazine(5a-i) were prepared per the proposed scheme. A new class of tetrazole heterocycles were synthesised and characterised. I n vivo analysis was carried out on the analgesic property of synthesised tetrazole derivatives (5a, 5b, 5c). Characterisation studies such as IR, 1H NMR, 13C NMR, Mass and elemental analysis were performed for the synthesised tetrazole derivatives. Some of the tetrazole derivatives 5a, 5b, and 5c were tested for anodyne activity using morphine as the standard drug. The data reveals that all the three compounds 5a, 5b and 5c taken for the study show analgesic activity by hot plate method and tail flick methods. Among tested compounds, compound 5c is found to have potent analgesic (anodyne) activity. The results of the study indicate that the sample taken for the study show fairly good business using morphine as the standard drug.

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

Computational and In-Vitro Validation of Natural Molecules as Potential Acetylcholinesterase Inhibitors and Neuroprotective Agents

2019 ◽  
Vol 16 (2) ◽  
pp. 116-127 ◽  
Author(s):  
Ashwani Kumar ◽  
Vineet Mehta ◽  
Utkarsh Raj ◽  
Pritish Kumar Varadwaj ◽  
Malairaman Udayabanu ◽  
...  
Keyword(s):  
In Silico ◽  
Hippocampal Neurons ◽  
Symptomatic Relief ◽  
In Vitro Assays ◽  
Disease Modifying Drugs ◽  
In Silico Docking ◽  
Ache Inhibitors ◽  
Significant Difference ◽  
Disease Modifying

Background: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer’s disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify new and safer ‘disease-modifying drugs’. Methods: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism. Further, the potential of the predicted molecules to inhibit acetylcholinesterase (AChE) activity and their ability to protect neurons from degeneration was determined through in-vitro assays. Results: Based on in-silico AChE interaction studies, we predicted quercetin, caffeine, ascorbic acid and gallic acid to be potential AChE inhibitors. We confirmed the AChE inhibitory potential of these molecules through in-vitro AChE inhibition assay and compared results with donepezil and begacestat. Herbal molecules significantly inhibited enzyme activity and inhibition for quercetin and caffeine did not show any significant difference from donepezil. Further, the tested molecules did not show any neurotoxicity against primary (E18) hippocampal neurons. We observed that quercetin and caffeine significantly improved neuronal survival and efficiently protected hippocampal neurons from HgCl2 induced neurodegeneration, which other molecules, including donepezil and begacestat, failed to do. Conclusion: Quercetin and caffeine have the potential as “disease-modifying drugs” and may find application in the management of neurological disorders such as AD.

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.

Synthesis and Biological Evaluations of Organoruthenium Scaffolds: A Comprehensive Update

2018 ◽  
Vol 15 (2) ◽  
pp. 179-207
Author(s):  
Ashaparna Mondal ◽  
Priyankar Paira
Keyword(s):  
Singlet Oxygen ◽  
Anticancer Agents ◽  
Ruthenium Complexes ◽  
Chemotherapeutic Agents ◽  
Quantum Yields ◽  
Ros Generation ◽  
Standard Drug ◽  
Cellular Environment ◽  
Theranostic Agents

Background: Currently ruthenium complexes are immerging as effective anticancer agents due to their less toxicity, better antiproliferative and antimetastatic activity, better stability in cellular environment and most importantly variable oxidation and co-ordination states of ruthenium allows binding this molecule with a variety of ligands. So in past few years researchers have shifted their interest towards organoruthenium complexes having good fluorescent profile that may be applicable for cancer theranostics. Nowadays, photodynamic therapy has become more acceptable because of its easy and effective approach towards killing cancer cells. Objective: Objective of this review article is to shed light on synthesis, characterization, stability and fluorescence studies of various ruthenium [Ru(II) and Ru(III)] complexes and different bioactivity studies conducted with the synthesized compounds to test their candidacy as potent chemotherapeutic agents. Methods: Various heterocyclic ligands containing N,O and S as heteroatom mainly were prepared and subjected to complexation with ruthenium-p-cymene moiety. In most cases [Ru(η6-p-cymene)(µ-Cl)Cl]2 was used as ruthenium precursor and the reactions were conducted in various alcohol medium such as methanol, ethanol or propanol. The synthesized complexes were characterized by 1H NMR and 13C NMR spectroscopy, GC-MS, ESI-MS, elemental analysis and single crystal X-ray crystallography methods. Fluorescence study and stability study were conducted accordingly using water, PBS buffer or DMSO. Stable compounds were considered for cell viability studies. To study the efficacy of the compounds in ROS generation as photosensitizers, in few cases, singlet oxygen quantum yields in presence of light were calculated. Suitable compounds were selected for in vitro & in vivo antiproliferative, anti-invasive activity studies. Result: Many newly synthesized compounds were found to have less IC50 compared to a standard drug cysplatin. Those compounds were also stable preferably in physiological conditions. Good fluorescence profile and ROS generation ability were observed for few compounds. Conclusion: Numerous ruthenium complexes were developed which can be used as cancer theranostic agents. Few molecules were synthesized as photosensitizers which were supposed to generate reactive singlet oxygen species in targeted cellular environment in presence of a particular type of light and thereby ceasing cancer cell growth.

Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

2019 ◽  
Vol 16 (4) ◽  
pp. 392-400 ◽  
Author(s):  
Göknil Pelin Coşkun ◽  
Teodora Djikic ◽  
Sadık Kalaycı ◽  
Kemal Yelekçi ◽  
Fikrettin Şahin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibacterial Activity ◽  
Enzyme Inhibitors ◽  
Binding Modes ◽  
Bacterial Strains ◽  
Urease Enzyme ◽  
H Pylori ◽  
Ulcer Treatment ◽  
Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today&#039;s standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2&#039;,4&#039;-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2&#039;,4&#039;-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2&#181;g/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

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