Glucopyranoside Dipentanoyl Esters: Synthesis, PASS Predication, Antimicrobial and In Silico ADMET Studies

2021 ◽  
Vol 13 (1) ◽  
pp. 221-235
Author(s):  
M. M. Matin ◽  
S. A. Chowdhury ◽  
M. M. H. Bhuiyan ◽  
S. M. A. Kawsar ◽  
M. A. Alam
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Direct Method ◽  
Macrophomina Phaseolina ◽  
Structure Activity ◽  
Activity Test ◽  
Antioxidant Agents ◽  
In Silico Admet

Dimolar pentanoylation of methyl α-D-glucopyranoside using direct method furnished the 2,6-di-O-pentanoate indicating regioselectivity at C-6 and C-2 positions. To develop glucopyranoside based potential antimicrobial agents, 2,6-di-O-pentanoate was further converted into eight newer 3,4-di-O-acyl esters reasonably in good yields. Both prediction of activity spectra for substances (PASS) and in vitro antimicrobial activity test established them as better antifungals than antibacterials. PASS predication also indicated that these sugar esters (SEs) are more potent as anticarcinogenic agents than as antioxidant agents. Structure activity relationship along with in silico ADMET studies clearly indicated that combination of pentanoyl (C5) and lauroyl (C12) in the glucopyranoside framework could be a potential antifungal agent especially against Macrophomina phaseolina.

scholarly journals In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 321 ◽  
Author(s):  
Ilinca Margareta Vlad ◽  
Diana Camelia Nuta ◽  
Cornel Chirita ◽  
Miron Teodor Caproiu ◽  
Constantin Draghici ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Maximum Tolerated Dose ◽  
In Vitro Cytotoxicity ◽  
Cell Membrane Permeability ◽  
Biofilm Growth

In a drug-repurposing-driven approach for speeding up the development of novel antimicrobial agents, this paper presents for the first time in the scientific literature the synthesis, physico-chemical characterization, in silico analysis, antimicrobial activity against bacterial and fungal strains in planktonic and biofilm growth state, as well as the in vitro cytotoxicity of some new 6,11-dihydrodibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds 7a–j) were confirmed by 1H-NMR, 13C-NMR and IR spectra, as well as by elemental analysis. The in silico bioinformatic and cheminformatic studies evidenced an optimal pharmacokinetic profile for the synthesized compounds 7a–j, characterized by an average lipophilic character predicting good cell membrane permeability and intestinal absorption; low maximum tolerated dose for humans; potassium channels encoded by the hERG I and II genes as potential targets and no carcinogenic effects. The obtained compounds exhibited a higher antimicrobial activity against the planktonic Gram-positive Staphylococcus aureus and Bacillus subtilis strains and the Candida albicans fungal strain. The obtained compounds also inhibited the ability of S. aureus, B. subtilis, Escherichia coli and C. albicans strains to colonize the inert substratum, accounting for their possible use as antibiofilm agents. All the active compounds exhibited low or acceptable cytotoxicity levels on the HCT8 cells, ensuring the potential use of these compounds for the development of new antimicrobial drugs with minimal side effects on the human cells and tissues.

Synthesis and Anti-HCV Activities of 18β-Glycyrrhetinic Acid Derivatives and Their In-silico ADMET analysis

2020 ◽  
Vol 16 ◽  
Author(s):  
Kai-Xia Zhang ◽  
Peng-Ru Wang ◽  
Fei Chen ◽  
Xi-Jing Qian ◽  
Lin Jia ◽  
...  
Keyword(s):  
In Silico ◽  
Active Metabolite ◽  
Structural Modification ◽  
Chemical Constituent ◽  
Glycyrrhetinic Acid ◽  
Lead Compound ◽  
Structure Activity ◽  
Ic50 Value ◽  
In Silico Admet

Background: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18β-Glycyrrhetinic acid (GA) is the main active metabolite of GL. Objective: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for promising lead compound for further identification of anti-HCV terpenoid candidate. Methods: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation, etc. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis were performed via “pkCSM” and “SwissADME” platforms. Results: Eighteen GA derivatives were synthesized and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with IC50 value of 0.79 μM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. Conclusion: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidate.

1,5-Benzodiazepine derivatives as potential antimicrobial agents: design, synthesis, biological evaluation, and structure–activity relationships

2015 ◽  
Vol 13 (19) ◽  
pp. 5497-5509 ◽  
Author(s):  
Lan-Zhi Wang ◽  
Xiao-Qing Li ◽  
Ying-Shuang An
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Benzodiazepine Derivatives

36 novel 1,5-benzodiazepine derivatives were synthesized and evaluated for their in vitro antimicrobial activity. The results revealed that most of the 1,5-benzodiazepine derivatives exhibited considerable potency against all of the tested strains.

scholarly journals Synthesis and Evaluation of Some New Thiazolidin-4-One Derivatives as Potential Antimicrobial Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
B. A. Baviskar ◽  
S. S. Khadabadi ◽  
S. L. Deore
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
Salmonella Typhi ◽  
Zone Of Inhibition ◽  
Structure Activity

A new series ofN-{4-methyl-5-[4-(4-oxo-2-phenyl(1,3-thiazolidin-3-yl)]-5-sulfanyl(1,2,4-triazol-3-yl)-1,3-thiazol-2-yl }acetamide (7a-l) was synthesized in order to determine their antimicrobial activity and feasible structure–activity relationships. The compounds were synthesized in good yield and the structures of all newly synthesized compounds were established on the basis of their IR,1HNMR, and elemental analysis. The synthesized compounds were testedin vitroantibacterial activity againstStaphylococcus aureus,Escherichia coli,Pseudomonas aeruginosaandSalmonella typhiand antifungal activity againstAspergillus niger,Candida albicansby measuring the zone of inhibition in mm.

scholarly journals ANTIMICROBIAL AND IN SILICO ADMET SCREENING OF NOVEL (E)-N-(2-(1H-INDOL-3-YL-AMINO) VINYL)-3-(1-METHYL-1H-INDOL-3-YL)-3-PHENYLPROPANAMIDE DERIVATIVES

2016 ◽  
Vol 8 (10) ◽  
pp. 251
Author(s):  
K. S. Manjunatha ◽  
N. D. Satyanarayan ◽  
S. Harishkumar
Keyword(s):  
In Silico ◽  
Antimicrobial Property ◽  
Quantitative Structure Activity Relationship ◽  
Pharmacokinetic Parameters ◽  
Antimicrobial Screening ◽  
Structure Activity ◽  
Amide Derivatives ◽  
In Silico Admet ◽  
Qsar Parameters

<p><strong>Objective: </strong>Synthesis, <em>in silico</em> absorption, distribution, metabolism, excretion, toxicity (ADMET) and <em>in vitro</em> antimicrobial screening of (<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3-phenylpropanamide derivatives.<strong></strong></p><p><strong>Methods: </strong>(<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3 phenylpropane-amide derivatives were synthesized by combining indole ethanolamine and substituted Meldrum’s adduct. The synthesized compounds were subjected to <em>in vitro</em> antimicrobial study by cup plate method and <em>in silico</em> ADMET properties using ACD/I-Lab 2.0.</p><p><strong>Results: </strong>The <em>in vitro </em>antimicrobial screening against precarious pathogenic microorganisms <em>viz</em>, <em>Pseudomonas aureginosa</em>, <em>Staphylococcus aureus,</em> <em>Escherichia coli, </em><em>Vibrio cholerae</em>, and the antifungal activity against <em>Candida albicans, </em><em>Aspergillus niger</em>, <em>Penicillin chrysogenum</em> and <em>Cladosporium oxysporum</em> strains. The results revealed that compounds 5b, 5c, 5d and 5e showed good antimicrobial property and obeyed the <em>in silico</em> pharmacokinetic parameters.</p><p><strong>Conclusion: </strong>The encouraging results exhibited by the compounds (<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3-phenyl propanamide derivatives, 5(a-e) can be explored as possible hits in antimicrobial therapy. The molecules obey the Lipinski rule of five when tested <em>in silico </em>and can be used in understanding the quantitative structure-activity relationship (QSAR) parameters.</p>

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

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