Bioprospecting Group, Agharkar Research Institute, Pune, Maharashtra, India.
Savitribai Phule Pune University, Pune, Maharashtra, India.
Nat Prod Res. 2022 Aug;36(15):3879-3886. doi: 10.1080/14786419.2021.1893317. Epub 2021 Mar 4.
The first synthetic route developed for Podocarflavone A reported from and its analogs in 7 steps. Computational analysis for binding with the pantothenate kinase (3AVO) of showed their docking score (ds) in the range of -8.9 to -9.3 Kcal/mol. MD simulations delineated the stability of the protein-ligand complexes in the TIP3P model. MMGBSA and MMPBSA values of were -42.46 Kcal/mol and -14.58 Kcal/mol, respectively. Further in-vitro antitubercular screening of compounds , , and against H37Ra using XRMA protocol exhibited promising antimycobacterial activity with IC values 21.82µg/mL, 15.55 µg/mL, and 16.56 µg/mL, respectively. Compounds , , and showed antibacterial activity with IC values 41.56 µg/mL, 24.72 µg/mL, and 72.45 µg/mL respectively against the . and showed inhibition with IC values 39.6 µg/mL and 27.64 µg/mL, respectively, against . The present study could help in the further development of lead molecules against tuberculosis.
从 报道的第 7 步合成路线首次开发了 Podocarflavone A 及其类似物。对与泛酸激酶（3AVO）结合的计算分析表明，它们的对接分数（ds）在-8.9 到-9.3 Kcal/mol 范围内。MD 模拟描绘了 TIP3P 模型中蛋白质-配体复合物的稳定性。的 MMGBSA 和 MMPBSA 值分别为-42.46 Kcal/mol 和-14.58 Kcal/mol。进一步使用 XRMA 方案对化合物 、 和 进行抗结核体外筛选，对 H37Ra 显示出有前途的抗分枝杆菌活性，IC 值分别为 21.82µg/mL、15.55µg/mL 和 16.56µg/mL。化合物 、 和 对 显示出抗菌活性，IC 值分别为 41.56µg/mL、24.72µg/mL 和 72.45µg/mL。和 对 的抑制活性分别为 IC 值 39.6µg/mL 和 27.64µg/mL。本研究有助于进一步开发抗结核的先导分子。
