The Impact of Fluorine and Piperazine on Norfloxacin's Toxicity: A Dual Study

Scientists explored how fluorine atoms and piperazine rings affect the toxicity of norfloxacin (NOR) and its degradation products (NOR-DPs). They used UV light and hydrogen peroxide (UV/H2O2) to break down NOR into eight smaller pieces (P1-P8). Interestingly, the toxicity levels against various cells like BV2, A549, HepG2, and Vero E6 cells didn't change much. However, when tested on fathead minnows, the degradation products showed increased mutagenicity and a higher median lethal concentration. In rats, the degradation products had lower bioaccumulation and oral median lethal doses.

To understand why, researchers used molecular docking to see how NOR-DPs interact with DNA gyrase A (gyrA). They found that specific amino acids like Ile13, Ser27, and Val28 played crucial roles through hydrogen bonds and hydrophobic interactions. The binding area (BA) and binding energy (BE) also changed slightly. Fluorine mainly affected BA, while the piperazine ring influenced both BA and BE. To predict the biotoxicity of NOR-DPs, scientists used something called "Yang ChuanXi Rules. " These rules consider molecular weight (MW), BA, BE, and a sum of two normalizations (η1 and η2) to estimate toxicity based on IC50, MIC50, and MBC50 values.

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