Four new α-pyrone derivatives, named germicidins P-S (1-4) along with nine known analogues (5-13) were discovered from the sponge-associated Streptomyces sp. 18A01 guided by Global Natural Products Social (GNPS) molecular networking, the LC-DAD-MS profile, and hexokinase II (HK2) inhibitory activity. The structures of 1-13 were elucidated by analysis of their HRMS, optical rotation, and NMR spectroscopic data. The absolute configurations of germicidin P (1) and germicidin Q (2) were determined on the basis of comparisons of experimental and theoretically calculated ECD spectra. Bioactivities of the isolated compounds were assayed against human HK2. The bioassay results showed that compounds 1-4 and 11-13 exhibited significant inhibitory activities against HK2, with IC₅₀ values ranging from 5.1 to 11.0 μM. A molecular docking simulation demonstrated that these germicidins were docked in the inner active site tunnel of HK2. Interestingly, the amino residue Arg91 has a better binding affinity and efficacy than the amino residue Asn89 in the process of HK2 binding to the ligands, resulting in better hexokinase inhibitory activity. This result provided a valuable perspective for better understanding their HK2 inhibition activity.

四个新的α吡喃酮衍生物，命名为germicidins PS（1 - 4与九个已知类似物（沿）5 - 13）从海绵相关发现链霉菌属。18A01 以全球天然产物社会 (GNPS) 分子网络、LC-DAD-MS 谱和己糖激酶 II (HK2) 抑制活性为指导。的结构1 - 13由他们的HRMS，旋光度，和NMR光谱数据的分析阐明。杀菌素 P ( 1 ) 和杀菌素 Q ( 2 )的绝对构型) 是在比较实验和理论计算的 ECD 光谱的基础上确定的。针对人HK2测定了分离化合物的生物活性。生物测定结果表明，化合物1 - 4 和11 - 13表现出显著抑制活性对HK2，用IC ₅₀值范围从 5.1 到 11.0 μM。分子对接模拟表明，这些杀菌素被对接在 HK2 的内部活性位点隧道中。有趣的是，在HK2与配体结合的过程中，氨基残基Arg91比氨基残基Asn89具有更好的结合亲和力和功效，从而产生更好的己糖激酶抑制活性。这一结果为更好地理解它们的 HK2 抑制活性提供了有价值的视角。