Ommi Ojaswitha, Dhopat Priyanka Sudhir, Sau Shashikanta, Estharla Madhu Rekha, Nanduri Srinivas, Kalia Nitin Pal, Yaddanapudi Venkata Madhavi
Work carried out at Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India.
Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER) Balanagar Hyderabad 500037 Telangana India
RSC Med Chem. 2024 Oct 22;16(1):420-8. doi: 10.1039/d4md00623b.
In our continued efforts to tackle antibiotic resistance, a new series of pyrazole-ciprofloxacin hybrids were designed, synthesized, and evaluated for their antibacterial activity against (), (), and (). Most of the compounds exhibited good to excellent activities against , and six compounds (7a, 7b, 7d, 7g, 7k, and 7p) exhibited higher or comparable activity (MIC = 0.125-0.5 μg mL) to ciprofloxacin (0.125 μg mL). Further, these selected compounds were non-toxic (CC ≥ 1000 μg mL) when evaluated for cell viability test against the Hep-G2 cell line. Three compounds (7a, 7d, and 7g) demonstrated excellent activity against ciprofloxacin-resistant with MIC values ranging from 0.125-0.5 μg mL and good antibiofilm activity. Among them, 7g displayed remarkable antibiofilm activity with an MBIC value of 0.02 μg mL, which is 50 times lower than ciprofloxacin (MBIC = 1.06 μg mL). A time-kill kinetics study indicated that 7g showed both concentration and time-dependent bactericidal properties. In addition, 7g effectively inhibited DNA-gyrase supercoiling activity at 1 μg mL (8× MIC). Two compounds 7b and 7d exhibited the highest activity against with a MIC of 0.5 μg mL, while 7c showed the highest activity against with a MIC value of 2 μg mL. Molecular docking studies revealed that 7g formed stable interactions at the DNA active site.
在我们持续对抗生素耐药性的努力中，设计、合成了一系列新型吡唑 - 环丙沙星杂合物，并评估了它们对（）、（）和（）的抗菌活性。大多数化合物对表现出良好至优异的活性，六种化合物（7a、7b、7d、7g、7k和7p）表现出与环丙沙星（0.125μg/mL）相当或更高的活性（MIC = 0.125 - 0.5μg/mL）。此外，在针对Hep - G2细胞系进行细胞活力测试时，这些选定的化合物无毒（CC≥1000μg/mL）。三种化合物（7a、7d和7g）对耐环丙沙星的表现出优异活性，MIC值范围为0.125 - 0.5μg/mL，且具有良好的抗生物膜活性。其中，7g表现出显著的抗生物膜活性，MBIC值为0.02μg/mL，比环丙沙星（MBIC = 1.06μg/mL）低50倍。时间 - 杀菌动力学研究表明，7g显示出浓度和时间依赖性杀菌特性。此外，7g在1μg/mL（8×MIC）时有效抑制DNA - 回旋酶超螺旋活性。两种化合物7b和7d对的活性最高，MIC为0.5μg/mL，而7c对的活性最高，MIC值为2μg/mL。分子对接研究表明，7g在DNA活性位点形成稳定相互作用。
