A New Reactive Ketenaminal: Synthesis, Coupling Reaction, Tautomeric Study, Docking and Antimicrobial Evaluation of the Products

2020 ◽  
Vol 16 (6) ◽  
pp. 761-773
Author(s):  
Huda K. Mahmoud ◽  
Hanadi A. Katouah ◽  
Marwa F. Harras ◽  
Thoraya A. Farghaly
Keyword(s):  
Binding Site ◽  
Antimicrobial Agents ◽  
Coupling Reaction ◽  
Docking Study ◽  
Binding Mode ◽  
Binding Energies ◽  
Simple Method ◽  
Antimicrobial Evaluation ◽  
New Compounds ◽  
Active Methylene

Background: One of the most successful reagents used in the synthesis of the reactive enaminone is DMF-DMA, but it is very expensive with harmful effects on the human health and reacts with special compounds to generate the enaminone such as active methylene centers. Aim: In this article, we synthesized a new ketenaminal by simple method with inexpensive reagents (through desulfurization in diphenylether). Methods: Thus, a novel reactive ketenaminal (enaminone) was synthesized from the desulfurization of 2-((2-(4-chlorophenyl)-2-oxoethyl)thio)-5,7-bis(4-methoxyphenyl)pyrido[2,3-d]pyrimidin- 4(3H)-one with diphenylether. The starting keteneaminal was coupled with diazotized anilines via the known coupling conditions to give a new series of 2-(4-chlorophenyl)-1-(2-(arylhydrazono)-2- oxoethyl)-5,7-bis(4-methoxy-phenyl)pyrido[2,3-d]pyrimidin-4(1H)-ones. Results: The structures of the new compounds were elucidated based on their IR, 1H-NMR, 13CNMR, and Mass spectra. Moreover, the potency of these compounds as antimicrobial agents has been evaluated. The results showed that some of the products have high activity nearly equal to that of the used standard antibiotic. Additionally, the docking study was done to get the binding mode of the synthesized compounds with the binding site of the DHFR enzyme. The results of molecular docking of the synthesized arylhydrazono compounds are able to fit in DHFR binding site with binding energies ranging from -4.989 to -8.178 Kcal/mol. Conclusion: Our goal was achieved in this context by the synthesis of new ketenaminal from inexpensive reagents, which was utilized in the preparation of bioactive arylhydrazone derivatives.

scholarly journals Synthesis and biological activity of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives

ADMET & DMPK ◽  
2021 ◽  
Author(s):  
Svetlana Meshcheryakova ◽  
Alina Shumadalova ◽  
Ozal Beylerli ◽  
Ilgiz Gareev
Keyword(s):  
Antimicrobial Agents ◽  
Biologically Active ◽  
Antibacterial And Antifungal Activities ◽  
Antibacterial Screening ◽  
Microbial Inhibition ◽  
Antimicrobial Evaluation ◽  
Temperature Interaction ◽  
Antibacterial And Antifungal ◽  
New Compounds ◽  
Base Object

The synthesis and antimicrobial evaluation of new 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives was investigated. According to the literature, there are a lot of antimicrobial agents among the pyrimidines and hydrazides, and therefore it seems promising to use 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide as a base object for synthesizing new biologically active substances. 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide was obtained by the hydrazinolysis of ethyl thioacetate, using a 3-fold molar excess of 85 % hydrazine hydrate in ethanol, at room temperature. Interaction of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]­acetohydrazide with ketones during boiling in ethanol yielded N-ylidenehydrazides. The solid obtained by concentration was collected, and then purified by recrystallization. The new compounds were characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The antibacterial and antifungal activities of the new compounds were analysed using agar diffusion and tenfold broth (pH 7.2 – 7.4) dilution methods, in comparison with the clinical used drugs, ceftriaxone and Pimafucin. The structure–activity studies showed that, depending on the nature of the hydrazide fragment, the newly synthesized compounds exhibited varying degrees of microbial inhibition. Within the same series the antimicrobial activity depends on the nature of the substituent attached to the benzene ring. The investigation of antibacterial screening data revealed that the compounds Nʹ-[1-(4-aminophenyl)ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1-(4-hydroxyphenyl)ethylidene]-2-[6-methyl-4-(thi­­etan­-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1- (2,5-dihydroxyphenyl) ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)-pyrimidin-2-ylthio]acetohydrazide were found to be more potent than the other synthesized analogues.

scholarly journals Synthesis, Characterization and Molecular Docking of 1,2,4-Triazole Derivatives as Potential Antimicrobial Agents

2020 ◽  
Vol 32 (6) ◽  
pp. 1437-1442
Author(s):  
Panneerselvam Kalaivani ◽  
Jayaraman Arikrishnan ◽  
Mannuthusamy Gopalakrishnan
Keyword(s):  
Antimicrobial Agents ◽  
Docking Study ◽  
Binding Mode ◽  
Zone Of Inhibition ◽  
Mass Spectral ◽  
Antibacterial And Antifungal Activities ◽  
Inhibition Concentration ◽  
Ft Ir ◽  
Antibacterial And Antifungal

In this study, a new series of (E)-N-(4-(3-(3,5-dialkylphenyl)acryloyl)phenyl)-2-(1H-1,2,4-triazol-1- yl)acetamide (32-41) was synthesized, characterized by FT-IR, 1H NMR, 13C NMR and Mass spectral analysis and evaluated for their in vitro antibacterial and antifungal activities. The docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of 1T9U protein. The zone of inhibition concentration was tested for the synthesized compounds against five bacterial and three fungal strains. Compounds 34 and 37 have good antibacterial activity. Compounds 3, 4 and 6 shows moderate inhibition against the antifungal activity.

scholarly journals Synthesis and antimicrobial evaluation of some 4-quinolinylazo-N-pyrimidinyl benzenesulfonamide derivatives

2019 ◽  
Vol 10 (1) ◽  
pp. 4846-4852
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Data ◽  
1H Nmr ◽  
Antimicrobial Agents ◽  
Chloroacetyl Chloride ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Chemical Structures ◽  
Antimicrobial Evaluation ◽  
New Compounds

Ten new compounds of quinoline clubbed with sulfonamide moiety were synthesized to be used as antimicrobial agents. Therefore, the diazotized N-(pyrimidin-2-yl)-benzenesulfonamide was diazocoupled with 8-hydroxyquinoline to furnish 4-(8-hydroxyquinolin-5-yl)-N-(pyrimidin-2-yl)benzenesulfonamide (3) which underwent chloroacetylation by chloroacetyl chloride to give the corresponding O-chloroacetylated product 6. The reactions of quinolinyl 2-chloroacetate derivative 6 with different nucleophiles (ethyl 2-mercaptoacetate, 2-mercapto-4,6-dimethylnicotinonitrile, o-aminothiophenol and/or malononitrile) were studied and utilized to pick up various heterocyclic systems 7, 10, 12 and 14. The chemical structures of newly prepared quinoline-containing scaffolds have been confirmed based on their spectral data (IR, 1H NMR and MS) and have been tested for their antimicrobial activity. The results showed that compounds 5d, 6, 7 and 14 displayed the highest activity against Gram-positive bacteria.

Molecular Modeling and Computer-Designing for New Compounds Starting From Thiazolidinedione Molecule as Anti-Hyperglycemics

2021 ◽  
Vol 14 (1) ◽  
pp. 5271-5277
Author(s):  
Mohamad Yahia Shikh Awad
Keyword(s):  
Virtual Screening ◽  
Binding Site ◽  
Docking Study ◽  
Test Set ◽  
Diabetic Type ◽  
Discovery Studio ◽  
Ppar Γ ◽  
Computer Designing ◽  
New Compounds

In the quest for novel PPAR-γ agonists as putative drugs  for the treatment of type 2 diabetes, a new test set  molecules were proposed as bioisosteric analogues to  the anti-diabetic thiazolidine-2, 5-diones (TZDs). Virtual  screening fitting study of these new molecules with the  generated discovery studio (DS) common feature PPAR-γ  agonist's hypothesis has predicted that most of these are  active as PPAR-γ agonist and hence they are as  antidiabetic-type 2 agents. Furthermore, molecular  docking virtual screening for these active compounds, with the binding site of the PPAR-γ enzyme, revealed that  the 2-pyrazolin-5-one and pyrazolidine-3,5-dione  derivatives have higher or similar docking scores like that  of the rosiglitazone. Also, the same docking study  revealed that these compounds have the same binding  site. This predicted that the designed proposed new  molecules are considered PPAR-γ agonists active, and  hence they are recommended to be synthesized as  potential anti-diabetic type-2 agents.  

scholarly journals An Efficient Synthesis of Thiophene Conjugated Benzothiazepines: in vitro Screening for their Antimicrobial Activity

2020 ◽  
Vol 32 (10) ◽  
pp. 2601-2605
Author(s):  
K.R. Raghavendra ◽  
P. Sudeep ◽  
K. Ajay Kumar ◽  
H.P. Jayadevappa
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Spectroscopic Studies ◽  
In Vitro Screening ◽  
Efficient Synthesis ◽  
Citrus Juice ◽  
E Coli ◽  
Antimicrobial Evaluation ◽  
New Compounds

A series of novel thiophene conjugated benzothiazepines were synthesized by the reaction of chalcones with 2-aminobenzenethiol in citrus juice medium. The new compounds were characterized by spectroscopic studies. Results of in vitro antimicrobial evaluation of newly synthesized compounds 5a-j shows that the compounds 5a and 5c have excellent antimicrobial inhibition in the range of 12.5-25.0 μg/mL against bacteria S. aureus, E. coli, P. aeruginosa and fungi A. niger, A. flavus organisms comparable to ciprofloxacin and nystatin and therefore these compounds might acts as lead molecules as antimicrobial agents.

scholarly journals Design, synthesis and docking study of acyl thiourea derivatives as possible histone deacetylase inhibitors with a novel zinc binding group

2019 ◽  
Author(s):  
Duraid H Al-Amily ◽  
Mohammed H Mohammed
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Docking Study ◽  
Binding Mode ◽  
Zinc Binding ◽  
Design Synthesis ◽  
Thiourea Derivatives ◽  
Low Cytotoxicity ◽  
New Compounds

Histone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed good cytotoxicity against cancer cells with low cytotoxicity against normal cells. Their binding mode to the active site of histone deacetylases have been studied by docking study.

Piroxicam Analogs: Design, Synthesis, Docking Study and Biological Evaluation as Promising Anti-HIV-1 agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Ali Imani ◽  
Sepehr Soleymani ◽  
Rouhollah Vahabpour ◽  
Zahra Hajimahdi ◽  
Afshin Zarghi
Keyword(s):  
Docking Study ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Hiv Integrase ◽  
Active Molecule ◽  
Design Synthesis ◽  
Molecule Docking ◽  
New Compounds ◽  
Anti Hiv ◽  
Hiv 1

Background: Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture. Objective: In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1- dioxide derivatives. Results: Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 M. Among them, compounds 7g was found to be the most active molecule. Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 M showed a similar binding mode to the HIV integrase inhibitors. Conclusion: Since all the compounds showed no remarkable cytotoxicity (CC50> 500 M), the designed scaffold is promising structure for development of new anti-HIV-1 agents.

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of New 2-mercaptoimidazoles (Series-III)

2019 ◽  
Vol 16 (5) ◽  
pp. 512-521 ◽  
Author(s):  
Nidhi Rani ◽  
Randhir Singh
Keyword(s):  
Sulfonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
One Pot ◽  
Design Synthesis ◽  
Toluene Sulfonic Acid ◽  
Antimicrobial Evaluation ◽  
Bacteria And Fungi ◽  
High Yields ◽  
Antimicrobial Potency

Background: A series of novel substituted 2-mercaptoimidazoles was synthesised efficiently and in high yields using one-pot synthesis from m-hydroxyacetophenones. Methods: The structures of the newly synthesized compounds were established, their molecular activity was investigated against some bacteria and fungi were further validated using molecular docking study. Results: Reaction of o-hydroxyphenacylbromide (2) with substituted aniline and KSCN, in the presence of catalyst p-toluene sulfonic acid afforded 4(a-r) in good yield. The structure of compounds (4a-r) was confirmed by IR, NMR and MS. Conclusion: The compounds exhibited excellent antimicrobial potency against the tested microorganism.

New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

2020 ◽  
Vol 17 (2) ◽  
pp. 124-137 ◽  
Author(s):  
Adel Mahmoud Attia ◽  
Ahmed Ibrahin Khodair ◽  
Eman Abdelnasser Gendy ◽  
Mohammed Abu El-Magd ◽  
Yaseen Ali Mosa Mohamed Elshaier
Keyword(s):  
Dna Damage ◽  
Anticancer Agents ◽  
Active Compound ◽  
Docking Study ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Antiviral Activities ◽  
Active Methylene ◽  
Damage Study

Background:Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.Objective:The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.Methods:A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.Results:The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.Conclusion:Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

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