scholarly journals Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

2020 ◽  
Vol 13 (7) ◽  
pp. 141 ◽  
Author(s):  
Gabriel Felipe Silva Passos ◽  
Matheus Gabriel Moura Gomes ◽  
Thiago Mendonça de Aquino ◽  
João Xavier de Araújo-Júnior ◽  
Stephannie Janaina Maia de Souza ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Chikungunya Virus ◽  
Cartilage Damage ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Biological Targets ◽  
Flow Cytometry Staining

Chikungunya virus (CHIKV) causes an infectious disease characterized by inflammation and pain of the musculoskeletal tissues accompanied by swelling in the joints and cartilage damage. Currently, there are no licensed vaccines or chemotherapeutic agents to prevent or treat CHIKV infections. In this context, our research aimed to explore the potential in vitro anti-CHIKV activity of acrylamide derivatives. In silico methods were applied to 132 Michael’s acceptors toward the six most important biological targets from CHIKV. Subsequently, the ten most promising acrylamides were selected and synthesized. From the cytotoxicity MTT assay, we verified that LQM330, 334, and 336 demonstrate high cell viability at 40 µM. Moreover, these derivatives exhibited anti-CHIKV activities, highlighting the compound LQM334 which exhibited an inhibition value of 81%. Thus, docking simulations were performed to suggest a potential CHIKV-target for LQM334. It was observed that the LQM334 has a high affinity towards the E3-E2-E1 glycoproteins complex. Moreover, LQM334 reduced the percentage of CHIKV-positive cells from 74.07 to 0.88%, 48h post-treatment on intracellular flow cytometry staining. In conclusion, all virtual simulations corroborated with experimental results, and LQM334 could be used as a promising anti-CHIKV scaffold for designing new drugs in the future.

scholarly journals Design, Synthesis and Antibacterial Activity of Coumarin-1,2,3-triazole Hybrids Obtained from Natural Furocoumarin Peucedanin

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2126 ◽  
Author(s):  
Alla V. Lipeeva ◽  
Danila O. Zakharov ◽  
Liubov G. Burova ◽  
Tatyana S. Frolova ◽  
Dmitry S. Baev ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Cycloaddition Reaction ◽  
Bacterial Strains ◽  
Design Synthesis ◽  
Docking Simulations ◽  
E Coli ◽  
Antibiotic Drugs ◽  
In Vitro Antibacterial Activity ◽  
Substituted Coumarins

Synthesis of 1,2,3-triazole-substituted coumarins and also 1,2,3-triazolyl or 1,2,3-triazolylalk-1-inyl-linked coumarin-2,3-furocoumarin hybrids was performed by employing the cross-coupling and copper catalyzed azide-alkyne cycloaddition reaction approaches. The synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, Bacillius subtilis, Actinomyces viscosus and Escherichia coli bacterial strains. Coumarin-benzoic acid hybrids 4с, 42с and 3-((4-acetylamino-3-(methoxycarbonyl)phenyl)ethynyl)coumarin (29) showed promising activity against S. aureus strains, and the 1,2,3-triazolyloct-1-inyl linked coumarin-2,3-furocoumarin hybrid 37c was endowed with high selectivity against B. subtilis and E. coli species. The in vitro antibacterial activity of 4с, 29, 37c and 42с can potentially be compared with that of a number of modern antibiotic drugs used in the clinic, suggesting promising prospects for further research. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations and the obtained results are quite promising.

Molecular Drug Design, Synthesis and Antibacterial study of Novel 4-Oxothiazolidin-3-yl Derivatives

2020 ◽  
pp. 1-10
Keyword(s):  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Design Synthesis ◽  
Gram Negative ◽  
Docking Simulations ◽  
Chemical Structures ◽  
Molecular Core ◽  
Diffusion Technique

New compounds containing 4-thiazolidinone pharmacophore 5(a) and (5b) have been synthesized. The chemical structures of the intermediate and final compounds were characterized and confirmed by using FT-IR and 1H-NMR spectroscopy. All final compounds were tested against gram-positive and gram-negative bacteria using a well-diffusion technique for their ability as antimicrobial agents. The tested compounds 5a and 5b showed variable and modest antibacterial activity against gram-negative bacteria and gram-positive bacteria. Molecular docking simulations were studied to understand the molecular core. The results were achieved by docking, the most active compounds into the active site of protein of the bacteria which completely accorded with in vitro results.

scholarly journals Design, Synthesis, Antihyperglycemic Studies, and Docking Simulations of Benzimidazole-Thiazolidinedione Hybrids

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Gutierréz-Hernández ◽  
Yelzyn Galván-Ciprés ◽  
Elix Alberto Domínguez-Mendoza ◽  
Yoshajandith Aguirre-Vidal ◽  
Samuel Estrada-Soto ◽  
...  
Keyword(s):  
Mrna Expression ◽  
In Silico ◽  
Knoevenagel Condensation ◽  
Binding Mode ◽  
Spectral Studies ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Step Procedure

A simple and cheap three-step procedure for the synthesis of three (5Z)-5-[3(4)-(1H-benzimidazol-2-ylmethoxy)benzylidene]-1,3-thiazolidine-2,4-diones has been described via a SN2 reaction of generally recognized as safe hydroxybenzaldehydes and 2-(chloromethyl)-1H-benzimidazole, followed by a Knoevenagel condensation with thiazolidine-2,4-dione in moderated yields. All the newly synthesized compounds were characterized using analytical and spectral studies. In vitro treatment on adipocytes with compounds increased the mRNA expression of two proteins recognized as strategic targets in diabetes: PPARγ and GLUT-4. In silico studies were conducted in order to explain the interaction binding mode of the synthesized compounds on PPARγ. In vivo studies confirmed that compounds 1–3 have robust antihyperglycemic action linked to insulin sensitization mechanisms. The present study provides three compounds with a promising antidiabetic action.

scholarly journals Design, Synthesis, Computational, and Preclinical Evaluation of natTi/45Ti-Labeled Urea-Based Glutamate PSMA Ligand

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1104 ◽  
Author(s):  
Kristina Søborg Pedersen ◽  
Christina Baun ◽  
Karin Michaelsen Nielsen ◽  
Helge Thisgaard ◽  
Andreas Ingemann Jensen ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Ex Vivo ◽  
Design Synthesis ◽  
Psma Ligand ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tumor Accumulation ◽  
Aided Design

Despite promising anti-cancer properties in vitro, all titanium-based pharmaceuticals have failed in vivo. Likewise, no target-specific positron emission tomography (PET) tracer based on the radionuclide 45Ti has been developed, notwithstanding its excellent PET imaging properties. In this contribution, we present liquid–liquid extraction (LLE) in flow-based recovery and the purification of 45Ti, computer-aided design, and the synthesis of a salan-natTi/45Ti-chelidamic acid (CA)-prostate-specific membrane antigen (PSMA) ligand containing the Glu-urea-Lys pharmacophore. The compound showed compromised serum stability, however, no visible PET signal from the PC3+ tumor was seen, while the ex vivo biodistribution measured the tumor accumulation at 1.1% ID/g. The in vivo instability was rationalized in terms of competitive citrate binding followed by Fe(III) transchelation. The strategy to improve the in vivo stability by implementing a unimolecular ligand design is presented.

scholarly journals Haemolytic potential of three chemotherapeutic agents and aspirin in glucose-6-phosphate dehydrogenase deficiency

1999 ◽  
Vol 5 (3) ◽  
pp. 457-464
Author(s):  
N. A. J. Ali ◽  
L. M. Al Naama ◽  
L. O. Khalid
Keyword(s):  
High Frequency ◽  
Dehydrogenase Deficiency ◽  
Local Population ◽  
Chemotherapeutic Agents ◽  
Red Cells ◽  
New Drugs ◽  
Local Variant ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Significant Concentration

The potential haemolytic effect of three chemotherapeutic drugs and aspirin was tested in vitro by gluthathione stability tests. Blood was collected from the local population of Basra, Iraq where previous studies had found a high frequency of glucose-6-phosphate dehydrogenase [G6PD] deficiency. Primaquine, chloramphenicol and sulfanilamide caused significant concentration-dependent reductions of glutathione levels in G6PD-deficient red cells when compared to normal red cells. Acetylsalicylic acid had no effect on glutathione level. The G6PD-deficient erythrocytes behaved as previously reported, probably due to similar patterns in the distribution of its variants. Studies on each local variant are warranted and new drugs should be tested for haemolytic potential prior to their introduction in areas where the deficiency is common

The Syntheses and Medicinal Attributes of Phenanthrenes as Anticancer Agents: A Quinquennial Update

2021 ◽  
Vol 28 ◽  
Author(s):  
Sarthak Jhingran ◽  
Kritika Laxmikeshav ◽  
Sayali Mone ◽  
Venkata Rao K ◽  
Nagula Shankaraiah
Keyword(s):  
Anticancer Agents ◽  
Chemotherapeutic Agents ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Base Pairs ◽  
Biological Targets ◽  
Carcinoma Cell Lines ◽  
Dna Base ◽  
Dna Base Pairs

: Cancer is a silent killer and remains to pose major health problems globally. Amongst the several biological targets, DNA is one of the most striking targets in cancer chemotherapy. Owing to its planar structure, phenanthrene and its derivatives exhibit potential cytotoxicity by intercalating between the DNA base pairs and by inhibiting the enzymes that are involved in the synthesis of DNA. However, due to the off-target effects and resistance, the development of novel chemotherapeutic agents would be meritorious. In this regard, we detail in the review on the development of phenanthrene-based derivatives reported in the last quinquennial. This review mainly focuses on the synthetic aspects and strategies to procure the fused phenanthrene derivatives such as (i) phenanthroindolizidines, phenanthroquinolizidine, phenanthroimidazoles, podophyllotoxin-based phenanthrenes and dihydrophenanthrodioxine derivatives, (ii) phenanthrene conjugates with other pharmacologically significant pharmacophores and (iii) phenanthrene-metal complexes. This review also edifies their potential in vitro cytotoxicity evaluation against various carcinoma cell lines in submicromolar to nanomolar ranges. Additionally, computational studies and structure-activity relationships (SARs) have also been presented to highlight the essential features of the designed congeners. Thus, this review would aid in the development of novel derivatives in future as potential cytotoxic agents in the field of medicinal chemistry.

Oxazolone–1,2,3-Triazole Hybrids: Design, Synthesis and Antimicrobial Evaluation

2018 ◽  
Vol 18 (17) ◽  
pp. 1506-1513 ◽  
Author(s):  
Kashmiri Lal ◽  
Lokesh Kumar ◽  
Ashwani Kumar ◽  
Anil Kumar
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Properties ◽  
Dilution Method ◽  
Antimicrobial Drugs ◽  
Activity Data ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Comparable Activity ◽  
Antimicrobial Evaluation

Background: Oxazolones and 1,2,3-triazoles are among the extensively studied heterocycles in medicinal chemistry. Both of these moieties are reported to possess a broad spectrum of biological activity including antimicrobial. Objective: The objective of the current work is to design, synthesize and antimicrobial evaluation of some new oxazolone-1,2,3-triazole hybrids. Methods: The designed oxazolone-1,2,3-triazole hybrids were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition. The antimicrobial evaluation was carried out using serial dilution method. Results: Most of the synthesized hybrids showed significant antimicrobial properties. Some of the compounds were found to be possessing better or comparable activity to that of the standards used. The docking simulations results are also in agreement with the antimicrobial activity data. Conclusion: Sixteen new hybrids were synthesized and tested in vitro for their antimicrobial activity. Some of the tested compounds exhibited promising antimicrobial activity and could be utilized for the development of the lead compounds for new and more potent antimicrobial drugs.

scholarly journals Design, Synthesis, and In Vitro Biological Activities of a Bio-Oxidizable Prodrug to Deliver Both ChEs and DYRK1A Inhibitors for AD Therapy

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1264 ◽  
Author(s):  
Anaïs Barré ◽  
Rabah Azzouz ◽  
Vincent Gembus ◽  
Cyril Papamicaël ◽  
Vincent Levacher
Keyword(s):  
Biological Activities ◽  
Kinetic Studies ◽  
Nmda Receptor Antagonist ◽  
New Drugs ◽  
Design Synthesis ◽  
Ache Inhibitors ◽  
Promising Target ◽  
Potent Inhibition ◽  
Approved Drugs

Despite their side effects, cholinesterase (ChE) inhibitors remain the only approved drugs to treat Alzheimer’s disease patients, along with the N-methyl-d-aspartate (NMDA) receptor antagonist memantine. In the last few years, the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has also been studied as a promising target for the development of new drugs for this pathology. In this context, and based on our previous characterization of bio-oxidizable prodrugs of potent acetylcholinesterase (AChE) inhibitors, we envisioned a strategy involving the synthesis of a bio-oxidizable prodrug of both ChE and DYRK1A inhibitors. To this end, we fixed our interest on a known potent inhibitor of DYRK1A, namely INDY. The designed prodrug of both ChE and DYRK1A inhibitors was successfully synthesized, connecting both inhibitors by a carbonate link. This prodrug and its corresponding drug were then evaluated as ChEs and DYRK1A inhibitors. Remarkably, in vitro results were in accordance with the starting hypothesis, showing a relative inactivity of the prodrug against DYRK1A and ChEs and a potent inhibition of ChEs by the oxidized form. Molecular docking and kinetic studies of ChE inhibition by the active compound are also discussed in this report.

scholarly journals Computer-aided design, synthesis, and characterization of molecular hybrids of dihydropyrazoles, aminopyrimidines, and thiazolidin-4-ones as potential inhibitors of the penicillin-binding protein 3 (PBP-3) of Escherichia coli

2021 ◽  
Vol 26 (1) ◽  
pp. 17-35
Author(s):  
Fabian Orozco-Lopez ◽  
Liliana Rocío Guerrero-Villalobos ◽  
Paola Andrea Cuervo-Pardo
Keyword(s):  
Computer Aided Design ◽  
Binding Protein ◽  
Docking Study ◽  
Computer Assisted ◽  
Penicillin Binding Protein ◽  
Molecular Docking Study ◽  
Spectra Analysis ◽  
Design Synthesis ◽  
Molecular Hybrids

A computer-assisted approach was used to model and study privileged heterocyclic scaffolds containing dihydropyrazole, pyrimidin-2-amine, and thiazolidin-4-one moieties (hybrid pharmacophores) to obtain novel and promising antimicrobial prototype molecules. Main bioavailability descriptors were determined in order to assess the drug-likeness of the designed compounds and to pre-filter eleven compounds exhibiting the best profiles, thus passing to molecular docking study against a key penicillin-binding protein type-3 from enterotoxygenic E. coli. Seven structures were chosen by theirenergies of affinity and docking interactions with key residues in the active site of the receptor. Seven compounds with the highest docking scores belonging to the series of chalcones, dihydropyrazoles, aminopyrimidines, and thiazolidin-4-ones were prepared via condensation or cyclocondensation reactions. The structural elucidation of the final products was carried out by infrared spectra analysis and NMR experiments. Such molecular hybrids considered as potential hits in the search for new antibacterial compounds will be tested in vitro in further studies.

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