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Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]pyrazole Derivatives as Potential Antibacterial Agents

Title: Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]pyrazole Derivatives as Potential Antibacterial Agents
Authors: Asgaonkar, Kalyani Dhirendra; Naik, Akshata Parashram; Ghate, Dipti Dattatrya; Shah, Parth Anil; Kachare, Shubham Sandeep; Rathod, Gajanan Pandit; Chitre, Trupti Sameer; Patil, Shital Manoj
Source: Current Topics in Chemistry ; volume 05 ; ISSN 2950-4023
Publisher Information: Bentham Science Publishers Ltd.
Publication Year: 2026
Description: Introduction: In the pursuit of new antibacterial agents, computational methods have gained significant traction. Computational studies have focused on the relationship between a molecule's chemical structure and its biological activity. The current study focuses on developing new antibacterial agents to address nosocomial S. aureus infections through the use of in silico methods and green synthesis techniques. Methods: Green synthesis methods such as stirring, microwave-assisted, and reflux techniques were utilized to prepare novel chemical entities (NCEs). NCEs are designed as pyrano[2,3- c]pyrazole derivatives based on the SAR study of pyran and pyrazole. ADMET analysis for drug-like properties, along with docking and MD simulation studies with DNA gyrase, guided the design of the NCEs. These NCEs were synthesized, characterized, and evaluated for antibacterial activity against S. aureus (compared to a standard drug). Results: All NCEs demonstrated characteristics typical of drug compounds, adhered to Lipinski's Rule of Five, and exhibited favorable docking scores with DNA gyrase, along with promising antibacterial activity against S. aureus. Discussion: Ten novel chemical entities were designed: B1-B5 and C1-C5. All NCEs demonstrated adherence to the Rule of Five. The screened NCEs B1-B5 were docked onto the crystal structures of DNA gyrase. The biological evaluation against S. aureus showed that these compounds produced larger zones of inhibition compared to Metronidazole under identical assay conditions. Conclusion: All the designed NCEs exhibited promising pharmacokinetic characteristics. Compounds C3, C2, and B2 demonstrated favorable docking scores with DNA gyrase and showed significant antibacterial activity.
Document Type: article in journal/newspaper
Language: English
DOI: 10.2174/0129504023394798250812051630
Availability: https://doi.org/10.2174/0129504023394798250812051630; https://www.eurekaselect.com/article/download/244684; https://www.eurekaselect.com/244684/article
Accession Number: edsbas.E6753F95
Database: BASE