Chemical descriptors, PASS, molecular docking, molecular dynamics and ADMET predictions of glucopyranoside derivatives as inhibitors to bacteria and fungi growth (original) (raw)
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Hacettepe Journal of Biology and Chemistry, 2015
B u çalışmada, metil 6-O-sinamoil-α-D-glukopiranozid türevlerinin yeni bir serisi, piridinde çeşitli açilleyici ajanlarla, metil α-D-glukopiranozid (1) tepkimesi ile-5 o C'da sentezlendi. Bu amaçla ilk olarak metil α-D-glukopiranosid in seçici sinamalasyonu, doğrudan asilasyon yöntemi ile gerçekleştirildi ve iyi bir verimle metil 6-O-sinamoil-α-D-glukopiranozid elde edildi. İkinci olarak, antimikrobiyal tarama çalışmaları için yeni ürünler elde etmek amacıyla, 6 sinamoil türevleri tek bir molekül çerçevesinde 2,3,4-triO -asil türevlerini içeren geniş fonkisyonel gruplara dönüştürüldü. Yeni sentezlenen bileşiklerin yapıları IR ve NMR ile karakterize edildi. Tüm bileşikler, gıda zehirlenmesi ve disk difüzyon yöntemleri kullanılarak in vitro ortamda antibakteriyel ve antifungal aktiviteleri açısından değerlendirildi. Çalışmada metil 6-O-sinamoil-2,3,4-triO -dekanoilα-D-glukopiranosid bileşiği hem Gram (+) B. subtilise hem de Gram (-) P. aeruginosa mikroorganizmasına karşı yüksek inhibisyon etkisi gösterdi. Test bileşiği, metil 6-O-sinamoil-2,3,4-triO -lauroil-α-D-glukopiranosid A ya karşı maksimum misel büyüme inhibisyonu sergiledi. Açillenmiş türevlerin fungal hattına karşı olan etkisinin bakteriyel patojenlere göre daha yüksek olduğu bulundu. Bu, seçilen patojenlere karşı seçilmiş kimyasalların antimikrobiyal etkisini gösteren ilk raporudur.
Acyl glucopyranosides: Synthesis, PASS predication, antifungal activities, and molecular docking
Organic Communications, 2022
Sugar esters (SEs) with fatty acyl chains showed diverse applications including antimicrobial inhibition against multidrug-resistant (MDR) microorganisms. Thus, fatty acid esters, especially 6-O-stearoyl glucopyranoside ester was prepared by the treatment of glucopyranoside with unimolar stearoyl chloride at low temperature. The 6-O-stearoyl ester thus obtained was further modified to four newer 2,3,4-O-acyl esters to incorporate decanoyl, lauroyl, palmitoyl, and benzoyl chains in the glucopyranoside skeleton. Prediction of activity spectrum for substances (PASS) analyses suggested that these fatty acid esters are more prone to fungal pathogens compared to bacterial pathogens. Guided by PASS analyses in vitro antifungal activities were screened against four fungal pathogens, which supported the PASS observation. To validate the findings molecular docking was conducted with lanosterol 14α-demethylase (CYP51), a significant fungal enzyme, which is the principal target of antifungal drugs. Corroboration of in vitro results with binding affinity revealed the possibility of glucopyranoside-based fatty acyl esters with stearoyl, decanoyl and lauroyl chains as highly potential compared to antifungal azole drugs.
Molecular Simulation
Our current study focuses on the molecular structures of the series of methyl 4,6-O-benzylidene-α-Dglucopyranoside 1-9 as potential antifungal agents to obtain more insight into the origin of their encouraging bioactivity. In vitro antimicrobial testing and the prediction of activity spectra for substances revealed that these carbohydrate derivatives have promising antifungal functionality compared to their antibacterial activities. In support of this finding, molecular docking was performed against lanosterol 14α-demethylase (CYP51A1) and Altemaria alternata (6LCC) by screening carbohydrate derivatives whereby significant binding affinities and non-bonding interactions have been observed against both microbial proteins. The majority of the derivatives studied here could bind near the critical catalytic residues. The molecular dynamics study has revealed that the complexes formed by these derivatives with the proteins lanosterol 14α-demethylase and Altemaria alternata can remain stable, both over time and in physiological conditions. The POM analysis shows the clear presence of an antifungal (O1 δ-O2 δ-) pharmacophore site. ADMET and QSAR predictions were analysed to assess their pharmacokinetic and drug-likeness properties, showing promising results in silico. This work demonstrates that potential carbohydrate derivatives bind to fungal pathogens in an effort to circumvent their activities and open avenues for the development of newer antibiotics, which may target fungal pathogens.
Journal of Bangladesh Academy of Sciences, 2014
Regioselective pentanoylation of methyl 4,6-O-(4-methoxybenzylidene)-?-D-glucopyranoside by the direct acylation method provided the methyl 4,6-O-(4-methoxybenzylidene)-2-O-pentanoyl- ?-D-glucopyranoside in good yield. A number of 3-O-acyl derivatives of this 2-O-pentanoylation product were also prepared in order to obtain new compounds and also gather additional information for structure elucidation. The chemical structure of the newly synthesized compounds was characterized by analytical and spectral methods. Synthesized acylated derivatives of Dglucopyranoside were screened for in vitro antimicrobial activities against ten human pathogenic bacteria and four plant pathogenic fungi. The study revealed that the acylated products exhibited moderate to good antimicrobial activities. It was interesting to observe that the selected compounds were more sensitive against fungal phytopathogens than those of the bacterial strains. DOI: http://dx.doi.org/10.3329/jbas.v37i2.17554 Journal of B...
Journal of Applied Science & Process Engineering, 2021
The present study describes different chemical reactivity predictions of 6-O-hexanoylation of octyl β-D-glucopyranosides prepared from octyl β-D-glucopyranoside (OBG). Also, molecular docking of the OBGs was conducted against SARS-CoV-2 main protease (6LU7), urate oxidase (Aspergillus flavus; 1R51) and glucoamylase (Aspergillus niger; 1KUL). DFT optimization indicated that glucoside 1 and its ester derivatives 2-7 exist in 4C1 conformation with C1 symmetry. Interestingly, the addition of ester group(s) decreased the HOMO-LUMO gap (Δԑ) of glucosides indicating their good chemical reactivities, whereas the other chemical reactivity descriptors indicated their moderate reactive nature. This fact of moderate reactivity was confirmed by their molecular docking with 6LU7, 1R51 and 1KUL. All the esters showed a moderate binding affinity with these three proteins. More importantly, incorporation of the ester group(s) increased binding affinity with 6LU7 and 1R51, whereas decreased with 1KUL...
2022
The present study is focused on the synthesis of methyl-4,6-O-benzylidene-α-D-glucopyranoside (MBG) derivatives and on the characterization of their biological properties. Their structures were revealed by spectroscopic characterization and antimicrobial activities were evaluated in vitro against human and plant microorganisms along with the prediction of substance activity spectra. Minimum inhibition concentration (0.675±0.01 to 1.35±0.01 mg/ml) and minimum bactericidal concentration (1.35±0.01 to 5.40±0.04 mg/ml) tests were conducted for two compounds (4 and 7) based on their activity. X-ray powder diffraction was employed for quantitatively identifying crystalline compounds. Molecular docking studies focused on fungal proteins and bacterial proteins where derivatives 3 and 6 exhibited very strong binding and inhibitory affinities. Also, the molecular dynamics study carried out revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and en...
Antimicrobial evaluation of methyl 4-O-Acetyl-α-L-Rhamnopyranoside derivatives
Chittagong University Journal of Biological Sciences, 2013
A number of 2,3-di-O-acyl derivatives (6-11) of methyl 4-O-acetyl-a-Lrhamnopyranoside (5) obtained by using various acylating agents were screened for in vitro antifungal activity against four plant pathogenic fungi, viz., Alternaria alternata, Curvularia lunata. Fusarium equiseti and Macrophomina phaseolina. These compounds were also screened for in vitro antibacterial activity against ten human pathogenic bacteria, viz., Bacillus subtilis, Bacillus cereus, Bacillus megaterium, Staphylococcus aureus, Escherichia coli, INABA ET (Vibrio), Pseudomonas species, Salmonella paratyphi, Shigella dysenteriae and Salmonella typhi. The study reveal that these 4-O-acetyl-?-L-rhamnopyranoside derivatives are more prone towards antifungal activities than that of antibacterial activities. DOI: http://dx.doi.org/10.3329/cujbs.v3i1.13404 The Chittagong Univ. J. B. Sci.,Vol. 3(1&2):33-43, 2008
Organic Communications, 2021
Black fungus is the foremost life-threatening disease during the SARS-CoV-2 affected patients and spreading quickly in the region of the subcontinent of India although there was no prescribed proper medication. As the Dglucofuranose and its derivatives are reported to show strong antifungal activity, this study has been designed with them for their computational investigation. Firstly, the overall prediction of activity spectra for substances (PASS) value illustrates a good probability to be active(Pa) and probability to be inactive (Pi) value. Next, pharmacokinetics parameters including drug-likeness and Lipinski's rules, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and overall quantum calculation of computational approaches by Density Functional Theory (DFT) have gradually been performed to analyze quantum calculations. After the analysis of docking score, it is found at-9.4 kcal/mol,-7.5 kcal/mol,-7.8 kcal/mol,-8.5 kcal/mol against the strain of black fungus protein strains Mycolicibacterium smegmatis, Mucor lusitanicus, Rhizomucor mieh, and white fungus protein Candida Auris, Aspergillus luchuensis and Candida albicans. Next, the molecular dynamics of docked complexes have been performed to check their stability in biological systems with water ranging 100 ns calculating the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) where the minimum RMSD and RMSF value indicated the higher stable configuration of docked complexes. These compounds have perfectly matched all the pharmacokinetics criteria to be a good drug candidate against both black and white fungus, and they are non-carcinogenic, low solubility, low toxic for both aquatic and non-aquatic. In addition, the quantum calculation using DFT conveys the strongest support and information about their chemical stability and biological significance. Finally, it could be concluded that the carboxylic group and methyl group in the benzene ring causes higher binding affinity against black and white fungus protein strain through the formation of hydrogen and hydrophobic bonds.
Synthesis And Characterization Of Methyl 4, 6-O-Enzylidene- ?-D-Glucopyranoside Derivatives
Journal of the Bangladesh Chemical Society, 2013
Regioselective benzoylation of methyl 4,6-O-benzylidene-?-D-glucopyranoside (1) using direct acylation method furnished the methyl 4,6-O-benzylidene-2-O-(4-t-butylbenzoyl)- ?-D-glucopyranoside (2) in an excellent yield. In order to obtain newer products for antimicrobial screening studies, the 2-O-4-t-butylbenzoyl derivative was further transformed to a series of 3-O-acyl derivatives (2-12) containing a wide variety of functionalities in a single molecular framework. Journal of Bangladesh Chemical Society, Vol. 25(2), 101-109, 2012 DOI: http://dx.doi.org/10.3329/jbcs.v25i2.15045
Molecular Docking Studies of Novel Aminopyrimidines as Potent Antifungal Agents
2019
Candida albicans is an opportunistic fungal pathogen that causes candidiasis in human hosts. Candidiasis includes a multitude of fungal infections, including invasive fungal infections, where most patients are immunocompromised; hence, the success of treatment is determined by the efficacy of the antifungal agent. However, with the increase in resistance to the existing drugs, the availability of effective antifungal agents is becoming scarce. Many pyrimidine derivatives exhibit powerful antifungal activity. In this study, In silico antifungal activity was carried out on twenty novel aminopyrimidine derivatives to identify the specificity of the pyrimidine analogues for the antifungal targets using ‘Glide’. Molecular docking studies were conducted on two antifungal targets; Dihydrofolate reductase of C. albicans (PDB ID: 4HOE); N-myristoyl transferase of C. albicans (PDB ID: 1IYK); energy minimization of title compounds was carried out using LigPrep, the protein targets were optimiz...