Development of pyrazolo[1,5-<i>a</i>]pyrimidine-based antibacterial agents

Mekky, Ahmed E. M.; Taha, N.; Mohammed, Nishil; Hussein, Fatma R. M.; Abdel‐Fattah, E.; El‐din, Ahmed S. Badr; Abdelsalam, A.; Sanad, Sherif M. H.

doi:10.1080/00397911.2023.2209815

Cited by 7 publications

(2 citation statements)

References 73 publications

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“…More attention has recently been drawn to avoiding the aforementioned resistance by increasing efforts to develop new and effective antibacterial agents [32,33] . Much effort has been made by our research group to prepare new azoloazines with promising antibacterial activity [34–39] . In this context, we reported herein the development of a three‐component protocol to synthesize arene‐linked pyrazolo[5,1‐ b ]quinazolines and their bis‐analogues (see Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Pyrazolo[5,1‐b]quinazolines and Their Bis‐analogues Linked to Different Spacers: Regioselective Synthesis, Antibacterial Screening and SwissADME Prediction Study

2023

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The regioselective synthesis of a new series of pyrazolo [5,1b]quinazolines was carried out using a three-component protocol. The protocol involved the reaction of the appropriate benzaldehydes, dimedone, and 1H-pyrazole-3,5-diamine in DMF at 150 °C. Using a similar protocol, three additional series of bis(pyrazolo[5,1-b]quinazolines), linked to different spacers, were prepared utilizing the respective bis(aldehydes). The new products showed a wide spectrum of antibacterial activity against six different the American Type Culture Collection (ATCC) bacterial strains. In general, p-xylene-linked bis(pyrazolo[5,1-b]quinazolines) had good antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 8.3 and 16.6 μM, respectively. Additionally, (4-nitrophenyl)-linked pyrazolo[5,1b]quinazoline had the best antibacterial activity with MIC/MBC values up to 2.1/4.3 μM. The Salmonella typhimurium reverse mutation assay (Ames mutagenicity test) was used to conclude that the (4-nitrophenyl)-linked product was not mutagenic to the Salmonella strains. Both the drug-likeness model score and the SwissADME predict the (4-nitrophenyl)-linked product's good physicochemical properties, and drug likeness.

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Section: Introductionmentioning

confidence: 99%

Pyrazolo[5,1‐b]quinazolines and Their Bis‐analogues Linked to Different Spacers: Regioselective Synthesis, Antibacterial Screening and SwissADME Prediction Study

2023

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“…In 2023, The Plastoquinone analogues synthesized by Mahmut Yildiz and team were composed of a modified quinone ring, connected to a piperidine moiety. The piperidine moiety was designed to enhance the overall efficacy of the analogues, and to improve their potential to act as antimicrobial agents (7,8) . In 2022, Abeer Hussein Ali conducted a groundbreaking investigation into the properties of a new Schiff base derivative of piperidine.…”

Section: Introductionmentioning

confidence: 99%

Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

Agrawal,

Patel,

Thakur

et al. 2023

IJST

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Objective: To explore the possibility of obtaining effective and harmless antibacterial drugs by conventional synthesis of new piperidine analogs. Methods: The target compound was carried out by cyclization reaction involving aromatic aldehydes and amine and further evaluated for their antimicrobiological assay using agar disc diffusion method. Computational investigation such as density functional theory (DFT) was carried out by B3LYP/6-31G (d,p) method to evaluate their electronic characteristics. Absorption, Distribution, Metabolism, and Excretion (ADME) properties were evaluated using the Swiss ADME server. The Antimicrobial activity was investigated using molecular docking and that molecule was prepared using MGL Tools 1.5.7. Auto Dock Vina 1.2.0. Findings: Among all the synthesized compounds 5a to 5h, compounds 5b and 5e showed good anti-bacterial properties against three pathogenic bacterial strains. B. subtilis is inhibited by compound 5b at a concentration of 26 mm. B. subtilis is inhibited by compound 5e at a concentration of 25 mm. Molecular Docking revealed that molecules 5b and 5e consistently showed a large binding affinity for all six target proteins, which was similar to that of the reference molecule, streptomycin. Drug-likeness predictions and the ADME analysis showed that most of the molecules do not violate any of the five Lipinski rule while some have only one or two violations, primarily because of high molecular weight. Novelty: In order to investigate the anti-bacterial impact of piperidine derivatives, a lot of work has been put into their synthesis and evaluation. These results might influence the creation and advancement of anti-microbial medication candidates that are more potent.

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Synthesis of New Bis(pyrazolo[1,5‐a]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors

Sanad

Abdelsalam

El‐din

et al. 2023

Chemistry & Biodiversity

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An efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5‐a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5‐a]pyrimidines) were prepared in 80–90 % yields by reacting the respective bis(enaminones) and 4‐(4‐substituted benzyl)‐1H‐pyrazole‐3,5‐diamines in pyridine at reflux temperature for 5–7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane‐ and butane‐linked bis(pyrazolo[1,5‐a]pyrimidines), which are attached to 3‐(4‐methyl‐ or 4‐methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 μM, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC50 values up to 7.2 μM.

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Development of pyrazolo[1,5-a]pyrimidine-based antibacterial agents

Cited by 7 publications

References 73 publications

Pyrazolo[5,1‐b]quinazolines and Their Bis‐analogues Linked to Different Spacers: Regioselective Synthesis, Antibacterial Screening and SwissADME Prediction Study

Pyrazolo[5,1‐b]quinazolines and Their Bis‐analogues Linked to Different Spacers: Regioselective Synthesis, Antibacterial Screening and SwissADME Prediction Study

Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

Synthesis of New Bis(pyrazolo[1,5‐a]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors

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