“…Using the MODELER 10.0 program, the target sequences were aligned with the downloaded template sequences and used to build as well as refine the 3D protein models. The best model was selected based on the least discrete optimized protein energy (DOPE) value. , The quality and accuracy of the predicted models were further analyzed using SAVES (), VoroMQA (), and ProSA () web servers. Each model was also visually inspected to ensure that it comprised the correct portion of the molecule under study.…”
Section: Methodsmentioning
confidence: 99%
“…The best model was selected based on the least discrete optimized protein energy (DOPE) value. 26 , 27 The quality and accuracy of the predicted models were further analyzed using SAVES ( ), VoroMQA ( ), and ProSA ( ) web servers. Each model was also visually inspected to ensure that it comprised the correct portion of the molecule under study.…”
Methicillin-resistant Staphylococcus aureus (MRSA)
is one of the leading causes of bacterial infections in both healthcare
and community settings. MRSA can acquire resistance to any current
antibiotic, which has major implications for its current and future
treatment options. As such, it is globally a major focus for infection
control efforts. The mechanical rigidity provided by peptidoglycans
in the bacteria cell walls makes it a promising target for broad-spectrum
antibacterial drug discovery. The development of drugs that can target
different stages of the synthesis of peptidoglycan in MRSA may compromise
the integrity of its cell wall and consequently result in the rapid
decline of diseases associated with this drug-resistant bacteria.
The present study is aimed at screening natural products with known in vitro activities against MRSA to identify their potential
to inhibit the proteins involved in the biosynthesis of the peptidoglycan
cell wall. A total of 262 compounds were obtained when a literature
survey was conducted on anti-MRSA natural products (AMNPs). Virtual
screening of the AMNPs was performed against various proteins (targets)
that are involved in the biosynthesis of the peptidoglycan (PPC) cell
wall using Schrödinger software (release 2020–3) to
determine their binding affinities. Nine AMNPs were identified as
potential multitarget inhibitors against peptidoglycan biosynthesis
proteins. Among these compounds, DB211 showed the strongest binding
affinity and interactions with six protein targets, representing three
stages of peptidoglycan biosynthesis, and thus was selected as the
most promising compound. The MD simulation results for DB211 and its
proteins indicated that the protein-ligand complexes were relatively
stable over the simulation period of 100 ns. In conclusion, DB211
showed the potential to inhibit six proteins involved in the biosynthesis
of the peptidoglycan cell wall in MRSA, thus reducing the chance of
MRSA developing resistance to this compound. Therefore, DB211 provided
a starting point for the design of new compounds that can inhibit
multiple targets in the biosynthesis of the peptidoglycan layer in
MRSA.
“…Using the MODELER 10.0 program, the target sequences were aligned with the downloaded template sequences and used to build as well as refine the 3D protein models. The best model was selected based on the least discrete optimized protein energy (DOPE) value. , The quality and accuracy of the predicted models were further analyzed using SAVES (), VoroMQA (), and ProSA () web servers. Each model was also visually inspected to ensure that it comprised the correct portion of the molecule under study.…”
Section: Methodsmentioning
confidence: 99%
“…The best model was selected based on the least discrete optimized protein energy (DOPE) value. 26 , 27 The quality and accuracy of the predicted models were further analyzed using SAVES ( ), VoroMQA ( ), and ProSA ( ) web servers. Each model was also visually inspected to ensure that it comprised the correct portion of the molecule under study.…”
Methicillin-resistant Staphylococcus aureus (MRSA)
is one of the leading causes of bacterial infections in both healthcare
and community settings. MRSA can acquire resistance to any current
antibiotic, which has major implications for its current and future
treatment options. As such, it is globally a major focus for infection
control efforts. The mechanical rigidity provided by peptidoglycans
in the bacteria cell walls makes it a promising target for broad-spectrum
antibacterial drug discovery. The development of drugs that can target
different stages of the synthesis of peptidoglycan in MRSA may compromise
the integrity of its cell wall and consequently result in the rapid
decline of diseases associated with this drug-resistant bacteria.
The present study is aimed at screening natural products with known in vitro activities against MRSA to identify their potential
to inhibit the proteins involved in the biosynthesis of the peptidoglycan
cell wall. A total of 262 compounds were obtained when a literature
survey was conducted on anti-MRSA natural products (AMNPs). Virtual
screening of the AMNPs was performed against various proteins (targets)
that are involved in the biosynthesis of the peptidoglycan (PPC) cell
wall using Schrödinger software (release 2020–3) to
determine their binding affinities. Nine AMNPs were identified as
potential multitarget inhibitors against peptidoglycan biosynthesis
proteins. Among these compounds, DB211 showed the strongest binding
affinity and interactions with six protein targets, representing three
stages of peptidoglycan biosynthesis, and thus was selected as the
most promising compound. The MD simulation results for DB211 and its
proteins indicated that the protein-ligand complexes were relatively
stable over the simulation period of 100 ns. In conclusion, DB211
showed the potential to inhibit six proteins involved in the biosynthesis
of the peptidoglycan cell wall in MRSA, thus reducing the chance of
MRSA developing resistance to this compound. Therefore, DB211 provided
a starting point for the design of new compounds that can inhibit
multiple targets in the biosynthesis of the peptidoglycan layer in
MRSA.
“…2 F) modified Sandmeyer’s method in which aniline or substituted aniline was treated with hydrochloride, chloral hydrate, sulfate, or salts of hydroxylamine, which was made in a solution of sodium sulfate and then cyclization reaction proceeded in the presence of conc. H 2 SO 4 [ 1 – 5 ]. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…Isatin and endogenous indoles have been found in the body fluids (adrenaline hormone) and mammalian tissues. It has been identified in urine, blood, and tissue using GC-MS and, more recently by HPLC with ultraviolet detector [ 1 , 2 ]. Plants of genuses such as Isatis tinctoria, Couroupita guianensisisatis, and Calanthe discolor [ 4 , 6 – 8 ] also contain isatin.…”
1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by reacting isatin with
o
-phenylenediamine. The synthesized compounds were structurally characterized and their
in-vivo
antimicrobial activity was tested against Gram-negative and Gram-positive bacteria using the inhibition zone method. Several newly synthesized isatin derivatives were found effective as antimicrobial agents and showed good potency (compounds
3c
,
3d
,
6a
,
6b
,
6d
). Compound
3c
displayed higher antimicrobial activity than standard drug (Amoxicillin) against
Staphylococcus aureus
at higher concentration (16 μg/mL) and against
Escherichia coli
at lower concentration (1 μg/mL).
“…Homology modelling is a powerful tool for understanding protein structures that have no solved structure. This approach is based on the principle that proteins with similar amino acid sequences have similar tertiary structures (Chahal et al ., 2020). Based on the three-dimensional structure model, it is possible to perform several analyses such as docking, screening and drug discovery; it is a useful technique since many ligands can be used in this field of study.…”
Aetiologic agents of diseases such as malaria and toxoplasmosis are found in representatives of the phylum Apicomplexa. Therefore, apicomplexan parasites are known to have a significant impact on public health. Epigenetic factors such as histone acetylation/deacetylation are among the main mechanisms of gene regulation in these parasites. Histone deacetylases (HDACs) have aroused a great deal of interest over the past 20 years for being promising targets in the development of drugs for treating several diseases such as cancer. In addition, they have also been shown to be effective for parasitic diseases. However, little is known about the structure of these proteins, as well as their interactions with specific ligands. In this paper, we modelled 14 HDACs from different apicomplexan parasites and performed molecular docking with 12 ligands analogous to the HDAC inhibitors FR235222 and apicidin, which had previously been tested against Toxoplasma gondii and Plasmodium falciparum. In this in silico study, we were able to gather relevant structural data regarding these proteins as well as insights into protein–ligand interactions for testing and developing drugs for these diseases.
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