ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Synthesis and antimicrobial activity of Sulfonyl-imidazole linked fused isoxazolo[3,4-b][1,2,3]triazolo[4,5-d]pyridines:PEG-400 mediated one-pot reaction under ultrasonic irradiation
Karukuri Premalathaa 1
Ravikumar Kapavarapu 2
Sridhar Kavela 3
Sirassu Narsimha 1
1. Department of Chemistry, Chaitanya (Deemed to be University), Hyderabad, India
2. Department of Pharmaceutical Chemistry and Phytochemistry, Nirmala College of Pharmacy, Mangalagiri, India
3. Department of Biotechnology, Chaitanya (Deemed to be University), Hyderabad, India
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Abstract
The rapid emergence of methicillin-resistant and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) represents a major global health challenge, necessitating the development of new antibacterial scaffolds with improved efficacy and safety. In this study, a novel series of sulfonyl-imidazole-linked fused isoxazolo [3,4-b][1,2,3]triazolo[4,5-d]pyridine derivatives (6a–6o) was synthesized using a PEG-400-mediated, ultrasound-assisted one-pot Cu(I)-catalysed strategy under environmentally benign conditions. The synthesized compounds were evaluated for antibacterial activity against MSSA, MRSA, and VRSA strains. Several derivatives exhibited potent antibacterial effects, with compound 6k emerging as the most active candidate, displaying MIC values of 1.56–3.12 µg/mL, surpassing the reference drug dicloxacillin. Selected compounds also demonstrated significant anti-biofilm activity, effectively inhibiting biofilm formation in resistant S. aureus strains. Importantly, hemolysis assays using mouse erythrocytes and cytotoxicity studies on RAW 264.7, THP-1, and BoMac cells revealed minimal hemolytic and cytotoxic effects, indicating excellent biocompatibility. Furthermore, immunomodulatory studies showed moderate and controlled cytokine induction, suggesting a balanced host immune response without excessive inflammation. Overall, this study identifies compound 6k as a promising lead with potent antibacterial, antibiofilm, and immunomodulatory properties coupled with a favorable safety profile, warranting further preclinical development against drug-resistant S. aureus infections.
Summary
Keywords
Antibacterial Agents, Antibiofilm activity, Isoxazolo-triazolopyridines, MRSA, TLR4 docking, Ultrasonication, VRSA
Received
09 January 2026
Accepted
20 February 2026
Copyright
© 2026 Premalathaa, Kapavarapu, Kavela and Narsimha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sridhar Kavela; Sirassu Narsimha
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