In-silico driven design and development of spirobenzimidazo-quinazolines as potential DNA gyrase inhibitors

Korrapati, Suresh Babu; Poornachandra, Y.; Pillai, Girinath G.; Mohammad, Faruq; Reddy, Venkata Ramana; Bhamidipati, Pranav; Amanchy, Ramars; Syed, Rabbani; Kamal, Ähmed

doi:10.1016/j.biopha.2020.111132

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…To commence the study, the protein structure of the DNA gyrase subunit b center (DNAG) (PDB: 1KZN) was obtained from the Protein Data Bank at a resolution of 2.3 Å. The frequent referencing of 1KZN in publications related to the antimicrobial field underscores its significance within the scientific community [39–41] . Ultra 10.0, a chemical drawing software, was used to develop the three‐dimensional molecule, and the resulting structure was saved in mol2 file format.…”

Section: Resultsmentioning

confidence: 99%

“…The frequent referencing of 1KZN in publications related to the antimicrobial field underscores its significance within the scientific community. [39][40][41] Ultra 10.0, a chemical drawing software, was used to develop the threedimensional molecule, and the resulting structure was saved in mol2 file format. For the docking simulations, SwissDock was chosen as the preferred docking engine in this study.…”

Section: Molecular Docking Studymentioning

confidence: 99%

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Synthesis of a Series of Quinoxaline Derivatives and Their Antibacterial Effectiveness Against Pathogenic Bacteria

Khatoon,

Abdul Malek,

Faudzi

et al. 2024

ChemistrySelect

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The pharmacological importance of quinoxaline derivatives in antibacterial research is well recognized. This study focuses on the synthesis of new 2,3‐dichloroquinoxaline derivatives containing thioether/ether groups to explore their potential as potent antibacterial agents against various pathogenic bacteria. Most of the compounds exhibited significant antibacterial properties comparable to the standard drug chlorhexidine (CHX). The derivatives of 2‐chloro‐3‐(arylthiol)quinoxaline demonstrated efficacy against Escherichia coli with minimum inhibitory concentrations (MIC) of 2.5 mg/mL and minimum bactericidal concentrations (MBC) of 2.5 to 5.0 mg/mL. These derivatives also showed similar sensitivity to Bacillus pumilus. In addition, molecular docking simulations were performed to investigate the interaction between the synthesized compounds and the DNA gyrase protein (PDB ID: 1KZN), a target for antibiotics. Among the synthesized compounds, 2,3‐bis(3‐nitrophenoxy)quinoxaline exhibited the most favourable docking score of −8.36 kcal/mol, with a binding affinity comparable to that of the reference ligand clorobiocin (−9.3 kcal/mol).

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Studymentioning

confidence: 99%

Synthesis of a Series of Quinoxaline Derivatives and Their Antibacterial Effectiveness Against Pathogenic Bacteria

Khatoon,

Abdul Malek,

Faudzi

et al. 2024

ChemistrySelect

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“…DNA gyrase and Topoisomerase IV are unique antibacterial therapeutic targets due to their ability to regulate bacterial DNA replication and topology. [11] In the search for novel DNA topoisomerase inhibitors, Kamal and co-workers introduced an integrative approach which entails computational prediction of binding sites and molecular modelling, followed by green synthesis and biological assessments of antibacterial activity of spirobenzimidazoquinazoline derivatives. The synthesized 5Hspiro[benzo [4,5]imidazo[1,2-c]quinazoline-6,3'-indolin]-2'-ones showed good to moderate activity against all the tested pathogenic bacterial strains (Figure 9).…”

Section: Antimicrobial Activitymentioning

confidence: 99%

“…[3][4][5][6] A wide spectrum of biological and therapeutic properties are shared by compounds with this motif, including anticonvulsant, antitumor, anti-inflammatory, antimicrobial, and anticancer activity (Figure 2). [7][8][9][10][11][12][13] Additionally, imidazo/benzimidazo [1,2-c]quinazoline scaffolds are also used in ions/molecular sensing and materials applications . [14][15][16][17][18] New synthetic techniques and applications for the Sustainable Development Goals (SDGs) have been reported in the literature throughout the last few decades.…”

Section: Introductionmentioning

confidence: 99%

An Extensive Analysis of Current Synthetic Methodologies and Applications of Imidazo/Benzimidazo[1,2‐c]Quinazolines

Bairy,

Sinha

2024

ChemistrySelect

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A great deal of attention has been received on developing N‐heterocyclic compounds due to their ambitious biological activities. Many of them are essential footstep to the development and discovery of new drugs. Imidazole/benzimidazole and quinazoline are essential pharmacologically active N‐heterocycles, and one of the molecular framework built up from their combination, imidazo/benzimidazo[1,2‐c]quinazoline, is of great attention in terms of synthesis, reactions, and medicinal applications. The positional variation of hetero N‐atoms and the functional groups acting as substituents in the main scaffold have a direct impact on the properties of imidazo/benzimidazo[1,2‐c]quinazolines. In addition to its physiological activities, this moiety is useful for electrical conductivity, molecules/ions sensing, coordination complex and coordination polymer (CP) formation, and their diverse applications. The major objective of this review is to highlight various synthetic approaches for imidazo/benzimidazo[1,2‐c]quinazolines motif since 2000. Toxicant‐free reaction conditions and the use of an extensive range of inexpensive substrates are two of the main practical benefits of the protocol in accomplishing the sustainable development goals.

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“…The spirooxindole-based structures are among the most vital nitrogen-containing compounds, particularly in the treatment of cancer due to the structural rigidity attributed to the spirocarbon present in these heterocycles 27–29 . However, spirooxindoles were reported to inhibit Topo I as well as Topo II enzymes 30 , 31 . In accordance with this, high interest was directed towards either discovering novel anticancer spirooxindole-based members or finding a simple and novel way to synthesise spirooxindoles.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

El-Kalyoubi,

Khalifa,

Abo-Elfadl

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC 50 of 0.042 and 1.172 μM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.

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In-silico driven design and development of spirobenzimidazo-quinazolines as potential DNA gyrase inhibitors

Cited by 11 publications

References 48 publications

Synthesis of a Series of Quinoxaline Derivatives and Their Antibacterial Effectiveness Against Pathogenic Bacteria

Synthesis of a Series of Quinoxaline Derivatives and Their Antibacterial Effectiveness Against Pathogenic Bacteria

An Extensive Analysis of Current Synthetic Methodologies and Applications of Imidazo/Benzimidazo[1,2‐c]Quinazolines

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

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