Design and Biological Evaluation of Furan/Pyrrole/Thiophene‐2‐carboxamide Derivatives as Efficient<scp>DNA</scp>GyraseB Inhibitors of<i>Staphylococcus aureus</i>

Renuka, Janupally; Medepi, Bhramam; Devi, Parthiban Brindha; Suryadevara, Priyanka; Jeankumar, Variam Ullas; Kulkarni, Pushkar; Yogeeswari, Perumal; Sriram, Dharmarajan

doi:10.1111/cbdd.12529

Cited by 16 publications

(14 citation statements)

References 23 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The derivatives of these compounds have been reported as efficient inhibitors against DNA gyrase B. 52 Moreover, studies have discussed the antitumor activity of various derivatives of thiophene-2-carboxamide, thiophene-3carboxamide, and furan-2-carboxamide. [52][53][54] In our work, we have prepared the core of these compounds with good yields as shown in the substrate scope, 9w, 9x, and 9u respectively.…”

Section: Resultsmentioning

confidence: 99%

Hydrogen bond mediated conversion of benzenenitriles and arylacetonitriles to amides: an “on/in-water” reaction strategy

2022

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Hydrogen bond mediated conversion of benzenenitriles and arylacetonitriles to amides: an “on/in-water” reaction strategy

2022

View full text Add to dashboard Cite

show abstract

“…Conversely, DNA gyrase is a type II topoisomerase enzyme necessary for maintaining topology and integrity during bacterial DNA replication and transcription [1]. It comprises four subunits (two As and two Bs) that are joined to produce a tetrameric holoenzyme [8]. The enzyme Gyr-A subunits bind to the DNA, and the Gyr-B subunits hydrolyze two ATP molecules to provide the whole enzyme complex with the energy required to relax DNA supercoils.…”

Section: Introductionmentioning

confidence: 99%

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli

et al. 2022

View full text Add to dashboard Cite

E. coli is a Gram-negative bacterium that causes different human infections. Additionally, it resists common antibiotics due to its outer protective membrane. Natural products have been proven to be efficient antibiotics. However, plant natural products are far less explored in this regard. Accordingly, over 16,000 structures covering almost all African medicinal plants in AfroDb in a structural-based virtual screening were used to find efficient anti-E. coli candidates. These drug-like structures were docked into the active sites of two important molecular targets (i.e., E. coli’s Ddl-B and Gyr-B). The top-scoring hits (i.e., got docking scores < −10 kcal/mol) produced in the initial virtual screening (0.15% of the database structures for Ddl-B and 0.17% of the database structures for Gyr-B in the database) were further refined using molecular dynamic simulation-based binding free energy (ΔG) calculation. Anthraquinones were found to prevail among the retrieved hits. Accordingly, readily available anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number of the tested derivatives demonstrated strong micromolar enzyme inhibition and antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging from 2 to 64 µg/mL. Moreover, both E. coli’s Ddl-B and Gyr-B were inhibited by emodin and chrysophanol with IC50 values comparable to the reference inhibitors (IC50 = 216 ± 5.6, 236 ± 8.9 and 0.81 ± 0.3, 1.5 ± 0.5 µM for Ddl-B and Gyr-B, respectively). All of the active antibacterial anthraquinone hits showed low to moderate cellular cytotoxicity (CC50 > 50 µM) against human normal fibroblasts (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried out to reveal the binding modes of these inhibitors inside the active site of each enzyme. The findings presented in this study are regarded as a significant step toward developing novel antibacterial agents against MDR strains.

show abstract

“…On the other hand, DNA gyrase is a topoisomerase-type enzyme that is required during bacterial DNA replication and transcription to maintain topology and integrity. It consists of four subunits (two A subunits and two B subunits) attached together to form a tetrameric holoenzyme [10]. Currently, DNA gyrase is considered one of the primary targets and has been clinically validated in most pathogenic bacteria.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Two Brominated Oxindole Alkaloids as Staphylococcal DNA Gyrase and Pyruvate Kinase Inhibitors via Inverse Virtual Screening

et al. 2020

View full text Add to dashboard Cite

In the present study, a small marine-derived natural products library was assessed for antibacterial potential. Among 36 isolated compounds, a number of bis-indole derivatives exhibited growth-inhibitory activity towards Gram-positive strains (Bacillus subtilis and multidrug-resistant Staphylococcus aureus). 5- and 6-trisindoline (5-Tris and 6-Tris) were the most active derivatives (minimum inhibitory concentration, MIC, 4–8 µM) that were subsequently selected for anti-biofilm activity evaluation. Only 5-Tris was able to inhibit the staphylococcal biofilm formation starting at a 5 µM concentration. In order to investigate their possible molecular targets, both natural products were subjected to in silico inverse virtual screening. Among 20 target proteins, DNA gyrase and pyruvate kinase were the most likely to be involved in the observed antibacterial and anti-biofilm activities of both selected natural products. The in vitro validation and in silico binding mode studies revealed that 5-Tris could act as a dual enzyme inhibitor (IC50 11.4 ± 0.03 and 6.6 ± 0.05 µM, respectively), while 6-Tris was a low micromolar gyrase-B inhibitor (IC50 2.1 ± 0.08 µM), indicating that the bromine position plays a crucial role in the determination of the antibacterial lead compound inhibitory activity.

show abstract

Design and Biological Evaluation of Furan/Pyrrole/Thiophene‐2‐carboxamide Derivatives as EfficientDNAGyraseB Inhibitors ofStaphylococcus aureus

Cited by 16 publications

References 23 publications

Hydrogen bond mediated conversion of benzenenitriles and arylacetonitriles to amides: an “on/in-water” reaction strategy

Hydrogen bond mediated conversion of benzenenitriles and arylacetonitriles to amides: an “on/in-water” reaction strategy

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli

Discovery of Two Brominated Oxindole Alkaloids as Staphylococcal DNA Gyrase and Pyruvate Kinase Inhibitors via Inverse Virtual Screening

Contact Info

Product

Resources

About