Computational Docking and in Silico Analysis of Potential Efflux Pump Inhibitor Punigratane

Rafiq, Zumaana; Sivaraj, Saranya; Vaidyanathan, Rama

doi:10.22159/ijpps.2018v10i3.21629

Cited by 9 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, the predicted binding affinity of ciprofloxacin for NorA was similar to that of other small multidrug resistance (SMS) efflux pumps with quinolones [19]. It does not escape to our attention that the residues Trp 293 , Tyr 131 , and Phe 47 of NorA could play a key role in the establishment of similar stabilizing interactions with aromatic drugs (Figure S4) [25].…”

Section: Resultsmentioning

confidence: 57%

A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters

et al. 2019

View full text Add to dashboard Cite

Multidrug efflux systems play a prominent role in medicine, as they are important contributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major facilitator superfamily that expels numerous drug compounds across the inner membrane of Staphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new opportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular modeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over 673 compounds from the PubChem database with a high (>80%) level of similarity to the chemical structure of capsaicin was used to study the binding affinity of small molecule compounds for the NorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in particular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of major facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy described in this study, and the structural information of the potential novel inhibitors thus identified, will stimulate others to pursue the development of better drugs to tackle multidrug resistance in S. aureus.

show abstract

Section: Resultsmentioning

confidence: 57%

A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The protein structure of alphasynuclein was retrieved from the protein data bank (PDB) website (www.rcsb.org) with a PDB ID: 1XQ8. The protein-ligand docking study was performed using AutoDock 4 software and the results are visualized using the PyMOL tool [27][28][29][30][31][32].…”

Section: Methodsmentioning

confidence: 99%

Anti-Parkinson Potential of Persea Americana Seed Extracts Through in-Silico Docking Study

EVANGELINE¹,

AHMED

2020

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objective: The aim of this study is to investigate the potential of Persea americana extracts for their Anti-Parkinson application through an in-silico docking study. Methods: PubChem and protein data bank databases were used to retrieve 3D structures. AutoDock4 was used to perform protein-ligand docking analysis. PyMOL was used to visualize the docking results. Results: Among the 30 ligand, the highest affinity was demonstrated by Hesperidin with a free binding energy of −6.8 kcal/mol and formation of five hydrogen bonds. The second highest significance was demonstrated by Biphenyl 4-(4-diethylaminobenzylidenamino) with a free binding energy of −5.9 kcal/mol with the formation of 2 hydrogen bonds. Among the three sets of phytochemicals from different solvent extracts, water extract demonstrated the highest potential as Anti-Parkinson active. Conclusion: P. americana extracts were analyzed for their Anti-Parkinson potential, and among the three extracts, the aqueous extract was predicted to have significant Anti-Parkinson potential, based on in silico docking analysis, due to the presence of active phytochemicals such as Hesperidin and others.

show abstract

“…Preparation of amides products (Ph An 1-10) [16]: In a carefully controlled experiment, an appropriate acid chloride with a mole ratio of 2.5 X 10 -3 was added dropwise to a mixture containing p-aminodiphenylamine and pyridine, both with mole ratios of 2.5 X 10 -3 in 5 ml dichloromethane. This addition process was CHEMICAL PROBLEMS 2024 no.…”

Section: Preparation Of Acid Chloride Derivativesmentioning

confidence: 99%

NEW p-AMINODIPHENYLAMINE AMIDE COMPOUNDS: DESIGN, SYNTHESIS AND ANTI β-lACTAMASES ACTIVITY EVALUATION

Saleh,

Mahmood

2024

Chemical Problems

View full text Add to dashboard Cite

β-Lactams, such as penicillins and cephalosporins, have long been recognized as the most effective antibiotics for the treatment of infectious diseases. However, the major limitation to their effectiveness is the bacterial production of β-lactamase enzymes, which hydrolyze the β-lactam ring in these drugs, rendering them inactive. To overcome this resistance mechanism, β-lactamase inhibitors, such as clavulanic acid, are commonly used in combination with β-lactams. By inhibiting the action of β-lactamase enzymes, these inhibitors restore the efficacy of β-lactam antibiotics. In recent studies, researchers have employed docking techniques to investigate the interaction between β-lactamase enzymes and potential inhibitors. Specifically, the β-lactamases TEM-1 (1pzp) and IMP-1 (1JJE) were used as targets for designing new compounds. A series of novel compounds were generated by synthesizing 6 amides compounds as acid chloride derivatives and reacting them with p-aminodiphenylamine to form amide bonds. These compounds were then characterized by the use of various physical and spectroscopic methods to confirm their structures. Next, the synthesized compounds were subjected to biological testing to evaluate their efficacy against β-lactamaseproducing Gram-positive and Gram-negative bacteria. This was accomplished by determining the minimum inhibitory concentration (MIC) of the compounds against three different strains of bacteria. Additionally, the possible anti β-lactamase activities of the compounds were compared to that of clavulanic acid. The results of this study revealed that five of the synthesized products exhibited effect similar to that of clavulanic acid for only one bacterial strain (Staph. aureus). Furthermore, the findings of the docking study suggest that the β-lactamase active pocket has a preference for hydrophobic substituents, as the synthesized products with these groups showed the highest binding score. In conclusion, the use of β-lactamase inhibitors, such as clavulanic acid, in combination with β-lactam antibiotics has proven effective in combating bacterial resistance. The development of novel compounds with anti β-lactamase activity holds promise for improving the treatment of infectious diseases. By understanding the preferences of the β-lactamase active pocket and designing compounds with hydrophobic substituents, researchers can enhance the affinity and efficacy of these inhibitors. This research contributes to the ongoing efforts to combat antibiotic resistance and improve patient outcomes in the field of infectious disease treatment.

show abstract

Computational Docking and in Silico Analysis of Potential Efflux Pump Inhibitor Punigratane

Cited by 9 publications

References 19 publications

A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters

A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters

Anti-Parkinson Potential of Persea Americana Seed Extracts Through in-Silico Docking Study

NEW p-AMINODIPHENYLAMINE AMIDE COMPOUNDS: DESIGN, SYNTHESIS AND ANTI β-lACTAMASES ACTIVITY EVALUATION

Contact Info

Product

Resources

About