scholarly journals Vibrational Properties of Benzoxaboroles and Their Interactions with Candida albicans’ LeuRS

Symmetry ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1845
Author(s):  
Ewa Kaczorowska ◽  
Agnieszka Adamczyk-Woźniak ◽  
Grażyna Zofia Żukowska ◽  
Paulina Kostecka ◽  
Andrzej Sporzyński
Keyword(s):  
Candida Albicans ◽  
Adenosine Monophosphate ◽  
Binding Pocket ◽  
Docking Studies ◽  
Vibrational Properties ◽  
Biological Functions ◽  
Intermolecular Hydrogen Bonds ◽  
Experimental Ir ◽  
The Past ◽  
Ir And Raman

Benzoxaboroles have emerged over the past decade mainly due to their growing medicinal importance. Regarding the wide application of IR spectroscopy in the pharmaceutical industry, the vibrational properties of over a dozen of benzoxaboroles were described, based on results of DFT calculations as well as IR and Raman spectra measurements. Investigated series of compounds included the currently available antifungal drug (Tavaborole, AN2690) as well as its derivatives. An intense and well-isolated band corresponding to the B-OH group stretching vibrations was present in all experimental IR spectra in the range of 1446–1414 cm−1 and can be considered as characteristic for benzoxaboroles. The vibrational properties of benzoxaboroles are shown to be affected by the formation of intramolecular as well as intermolecular hydrogen bonds, which should also influence the interactions of benzoxaboroles with biomolecules and impact on their biological functions. Docking studies of the benzoxaboroles’ adenosine monophosphate (AMP) spiroboronates into the Candida albicans leucyl-RS synthetase binding pocket showed that the introduction of an amine substituent has a strong influence on their binding. The determined values of inhibition constants manifest high potential of some of the investigated molecules as possible inhibitors of that enzyme.

scholarly journals Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

2015 ◽  
Vol 59 (4) ◽  
pp. 2153-2168 ◽  
Author(s):  
B. N. Singh ◽  
D. K. Upreti ◽  
B. R. Singh ◽  
G. Pandey ◽  
S. Verma ◽  
...  
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Apoptotic Cell ◽  
Hyphal Growth ◽  
Binding Pocket ◽  
Docking Studies ◽  
Apoptotic Cell Death ◽  
Content Type ◽  
Dose Dependent

ABSTRACTQuorum sensing (QS) regulates group behaviors ofCandida albicanssuch as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced byC. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment ofC. albicansinfections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnealongissima), can be implemented as a sensitizing agent for FCZ-resistantC. albicansNBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy ofC. albicansinfections.

scholarly journals Synthesis, Properties and Antimicrobial Activity of 5-Trifluoromethyl-2-formylphenylboronic Acid

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 799 ◽  
Author(s):  
Agnieszka Adamczyk-Woźniak ◽  
Jan T. Gozdalik ◽  
Dorota Wieczorek ◽  
Izabela D. Madura ◽  
Ewa Kaczorowska ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Bacillus Cereus ◽  
Title Compound ◽  
Phenylboronic Acid ◽  
Binding Pocket ◽  
Docking Studies ◽  
Trna Synthetase

2-Formylphenylboronic acids display many interesting features, not only from synthetic but also from an application as well as structural points of view. 5-Trifluoromethyl-2-formyl phenylboronic acid has been synthesized and characterized in terms of its structure and properties. The presence of an electron-withdrawing substituent results in a considerable rise in the acidity in comparison with its analogues. In some solutions, the title compound isomerizes with formation of the corresponding 3-hydroxybenzoxaborole. Taking into account the probable mechanism of antifungal action of benzoxaboroles, which blocks the cytoplasmic leucyl-tRNA synthetase (LeuRS) of the microorganism, docking studies with the active site of the enzymes have been carried out. It showed possible binding of the cyclic isomer into the binding pocket of Candida albicans LeuRS, similar to that of the recently approved benzoxaborole antifungal drug (AN2690, Tavaborole, Kerydin). In case of Escherichia coli LeuRS, the opened isomer displays a much higher inhibition constant in comparison with the cyclic one. The antimicrobial activity of the title compound was also investigated in vitro, showing moderate action against Candida albicans. The compound reveals higher activity against Aspergillus niger as well as bacteria such as Escherichia coli and Bacillus cereus. In case of Bacillus cereus, the determined Minimum Inhibitory Concentration (MIC) value is lower than that of AN2690 (Tavaborole). The results confirm potential of 2-formylphenylboronic acids as antibacterial agents and give a hint of their possible mechanism of action.

Comparison and Analysis of Computational Methods for Identifying N6 - methyladenosine Sites in Saccharomyces Cerevisiae

2020 ◽  
Vol 26 ◽  
Author(s):  
Pengmian Feng ◽  
Lijing Feng ◽  
Chaohui Tang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Computational Methods ◽  
Computational Analysis ◽  
Computational Prediction ◽  
Experimental Methods ◽  
Biological Processes ◽  
Biological Functions ◽  
Precise Location ◽  
Future Directions ◽  
The Past

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.

scholarly journals A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells

2021 ◽  
Author(s):  
Rashmi Kumari ◽  
Vasumathy R ◽  
Dhanya Sunil ◽  
Raghumani Singh Ningthoujam ◽  
Badri Narain Pandey ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Tumor Hypoxia ◽  
Binding Pocket ◽  
Docking Studies ◽  
Single Step ◽  
Naphthalic Anhydride ◽  
Hypoxic Conditions ◽  
Fluorescence Measurements ◽  
Enzymatic Reduction

AbstractThe bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract

scholarly journals Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

2015 ◽  
Vol 10 (4) ◽  
pp. 917 ◽  
Author(s):  
Mukesh Kumar Kumawat ◽  
Dipak Chetia
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Activity Screening

<p class="Abstract">Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of <em>Plasmodium falciparum</em> (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.</p><p> </p>

scholarly journals Experimental and theoretical study of Aspartic acid

2019 ◽  
Keyword(s):  
Aspartic Acid ◽  
Single Molecule ◽  
Dft Calculation ◽  
Theoretical Study ◽  
Quantum Mechanical ◽  
Experimental Ir ◽  
Vibrational Bands ◽  
Computational Research ◽  
Ir And Raman ◽  
Dielectric Environment

The aim of this research is to detect zwittterionic structure of the aspartic acid and confirm the experimental spectra with quantum chemical calculations. The experimental IR and Raman spectra of aspartic acid powder show no vibrational bands of OH and NH stretching in expected spectral region. We assume that zwitterionic structure of aspartic acid is responsible for lowering the frequencies of these vibrations. An extensive experimental and computational research supports this assumption. Our DFT calculation strongly suggests the need for the dielectric environment in order to stabilize the zwitterionic structure of a single molecule. The network of intermolecular hydrogen bonding between aspartic acid molecules provides this dielectric environment. The DFT quantum mechanical calculations corroborate this assumption by optimizing a four-member group of molecules, which also gives an explanation of broad IR spectrum lines.

scholarly journals PHYTOCHEMICALS AS POTENTIAL INHIBITORS OF LANOSTEROL 14 Α-DEMETHYLASE (CYP51) ENZYME: AN IN SILICO STUDY ON SIXTY MOLECULES

2020 ◽  
pp. 18-30
Author(s):  
ASHWINI KHANDERAO JADHAV ◽  
PATHAN KAMRAN KHAN ◽  
SANKUNNY MOHAN KARUPPAYIL
Keyword(s):  
Hydrogen Bond ◽  
Candida Albicans ◽  
Docking Study ◽  
Docking Studies ◽  
Antifungal Drugs ◽  
Ergosterol Biosynthesis ◽  
Binding Residue ◽  
Therapeutic Drugs ◽  
Ergosterol Synthesis ◽  
Potential Inhibitors

Lanosterol 14 α-demethylase (CYP51) is a key protein involved in ergosterol biosynthesis of Candida albicans and a crucial target for ergosterol synthesis inhibition. However, in the last two decades drug resistance is reported under clinical situations to most of the prescribed antifungal drugs like azole group of drugs. In this study, molecular docking of sixty plant molecules with Lanosterol 14 α-demethylase protein has been done. The homology modeling tool PHYRE2 was used to predict the structure of Lanosterol 14 α-demethylase. Predicted structure was used for docking studies with sixty plant molecules by using Autodock 1.5.6 cr2™. Among the sixty plant molecules, forty-seven were found to form hydrogen bond and the rest of the plant molecules did not form a hydrogen bond with Lanosterol 14 α-demethylase. Docking study of a library of sixty molecules revealed that 48 plant molecules showed an excellent and good binding affinity with predicted protein model Lanosterol 14 α-demethylase of Candida albicans. The binding residue comparison of docked molecules with that of Ketoconazole revealed, fourteen molecules have similar binding residue. These fourteen molecules may have a similar mode of action as that of Ketoconazole. These molecules should be screened and used to discover new antifungal therapeutic drugs.

scholarly journals Synthesis, Molecular Docking Studies and Antifungal Activity Evaluation of New Thiazolyl-methylen-1,3,4-oxadiazolines as Potential Lanosterol 14a-demethylase Inhibitors

2019 ◽  
Vol 70 (10) ◽  
pp. 3522-3526
Author(s):  
Smaranda Oniga ◽  
Catalin Araniciu ◽  
Gabriel Marc ◽  
Livia Uncu ◽  
Mariana Palage ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Activity Evaluation ◽  
Lanosterol Demethylase ◽  
Target Enzyme

Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen-1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors. The final compounds were screened for antifungal activity against the Candida albicans ATCC 90028 strain. Molecular docking studies were performed to investigate the interaction modes between the compounds and the active site of lanosterol 14a-demethylase, which is a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for the final compounds 5a-h.

scholarly journals Inhibition of Phosphodiesterase 5 Enzyme by Pterine- 6 Carboxylic Acid from Baphia nitida –Related to Erectile Dysfunction: Computational Kinetic

2020 ◽  
pp. 49-55
Author(s):  
Wopara, Iheanyichukwu ◽  
S. K. Mobisson ◽  
Egelege Aziemeola Pius ◽  
A. A. Uwakwe ◽  
M. O. Wegwu
Keyword(s):  
Erectile Dysfunction ◽  
Carboxylic Acid ◽  
Active Site ◽  
In Silico ◽  
Binding Pocket ◽  
Docking Studies ◽  
Drug Candidate ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Phosphodiesterase 5

Treatment of erectile dysfunction is associated with inhibition of Phosphodiesterase 5 enzyme. This study deals with the evaluation of Pterin-6-carboxylic acid inhibitory activity on phosphodiesterase 5 (PDB ID: 4OEW) using in silico docking studies. Pterin-6-carboxylic acid from Baphia nitida was isolated using GC-MS and docked into PDE5 active site. The docking result showed that pterin-6-carboxylic acid bind to the active site of phosphodiesterase 5 with the binding energy value of -7.1 and 2.05A° - 2.23A° when compared with other compound found in the plant. Moreso, docking analysis with the ligand identified specific residues such as: Ile 778, Phe 820, Gln 817, Ser 815 and Gln 775 within the binding pocket which played an important role in the ligand binding affinity to the protein. Result from our In silico studies hypothesized that pterin-6-carboxylic acid can be an inhibitory agent for PDE5 protein which could be a potential drug candidate for the treatment of erectile dysfunction.

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