{"doi":"10.1016/j.microb.2025.100343","title":"ZAB260: A novel and potent antibacterial agent targeting DNA gyrase","abstract":"DNA gyrase and topoisomerase IV are well-established targets for antibiotics. These enzymes play crucial roles in managing the topology of DNA, which is essential for bacterial survival. ZAB260, an inhibitor of bacterial DNA gyrase, is a dihydroquinoline carbonitrile-based antibacterial agent, which has potent antimicrobial activity against susceptible and drug-resistant pathogens. The MIC 90 for ZAB260 against methicillin resistant S. aureus , S. pyogens , S. pneumoniae , E . coli and A. baumannii were observed at 0.125 µg/ml, 0.25 µg/ml, 1 µg/ml, 2 µg/ml and 2 µg/ml respectively. The in vitro activity was evaluated using time-kill kinetics, post-antibiotic effect (PAE), and sub-inhibitory effect. The time-kill curves could show the bactericidal activity at 4X and 8X MIC at 24 h against S. aureus and A. baumannii . The post-antibiotic effect was modest when it was tested against S. aureus (2 h) and A. baumannii (4 h). The PAE and sub-MIC effect (SME) for S. aureus and A. baumannii was extended for 16 h and > 8 h. Checkerboard analysis of ZAB260 with marketed antimicrobials (Tetracycline, Levofloxacin, Cefepime, Azithromycin, Colistin, Meropenem) showed additive effect against A. baumannii . ZAB260 was also tested in rat lung infection model at 6.25, 12, 25, 50 and 100 mg/kg dose and a dose dependent reduction in log CFU was observed. Thus, ZAB260 was identified as a bactericidal agent with moderate post-antibiotic effect (PAE) and an extended PAE-sub-MIC effect (PAE-SME). It also showed a reduction of over 4 log CFU in rat lung infection model. These findings warrant further investigation for potential use in treating infections caused by these pathogens. • NBTIs binds to the site different from quinolones, hence would evade the existing quinolone induced resistance. • ZAB260 demonstrated potent antibacterial activity against MDR strains (active against both A. baumannii and S. aureus ). • ZAB260 showed dose dependent reduction in log CFU in rat lung infection model model.","journal":"The Microbe","year":2025,"id":564437,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1467780,"name":"Bhaumin Patel","orcid":null,"position":1,"is_corresponding":false},{"id":1467781,"name":"Jinal Trivedi","orcid":null,"position":2,"is_corresponding":false},{"id":1467448,"name":"Purvi Vyas","orcid":"0009-0009-3197-2711","position":3,"is_corresponding":false},{"id":1467782,"name":"Vishwanath Pawar","orcid":null,"position":4,"is_corresponding":false},{"id":1467449,"name":"Poonam Giri","orcid":"0000-0003-4347-5113","position":5,"is_corresponding":false},{"id":1467783,"name":"S Sachchidanand","orcid":null,"position":6,"is_corresponding":false},{"id":1467784,"name":"Kasinath Viswanathan","orcid":null,"position":7,"is_corresponding":false},{"id":1467450,"name":"Rajiv Sharma","orcid":"0000-0002-1905-0986","position":8,"is_corresponding":false},{"id":1467785,"name":"Mukul Jain","orcid":null,"position":9,"is_corresponding":false},{"id":1467786,"name":"Pravin S. Iyer","orcid":null,"position":10,"is_corresponding":false},{"id":1467451,"name":"Jigar Desai","orcid":"0000-0001-6932-6576","position":11,"is_corresponding":false},{"id":1173563,"name":"Sanjay Kumar","orcid":"0009-0002-5574-5547","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:56:20.933088Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}