Abstract

In this study, acetovanillone-derived novel benzyl ethers were synthesized as target compounds. For the synthesis of these target compounds, ketone derivatives (3a–b) were synthesized as the starting compounds. Compounds 4a–b, which are alcohol derivatives, were then synthesized from the reduction of these ketone derivatives. In the last stage of the synthesis study, benzyl ether derivatives (6a–h, 7a–h), the target compounds containing acetovanillone, were synthesized from the reaction of the alcohol derivatives (4a–b) with various benzyl halides (5a–h). The structures of the synthesized compounds were characterized by various spectroscopic methods (FT-IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis). In vitro antileishmanial and antibacterial activity tests were then performed for all synthesized compounds. Biological activity tests showed that while only a few of the compounds had antileishmanial activity, most had antibacterial activity. In addition, the ADME parameters, pharmacokinetic properties, and drug-like nature of all compounds were theoretically investigated using the SwissADME webserver. Finally, molecular docking simulations were carried out to support in vitro investigations and evaluate the inhibition effect of the synthesized compounds on the 3IW2 (Mycobacterium tuberculosis (Mtb) Cyp125; Pdb ID: 3IW2) receptor structure. Also, possible binding sites of some compounds with high affinity to Mtb Cyp125 according to docking results were identified.

摘要

在这项研究中，合成了乙酰香草酮衍生的新型苄基醚作为目标化合物。为了合成这些目标化合物，合成了酮衍生物 ( 3a-b ) 作为起始化合物。化合物4a-b是醇衍生物，然后由这些酮衍生物的还原合成。在合成研究的最后阶段，由醇衍生物（4a-b）与各种苄基卤化物（5a-h ）反应合成了含有乙酰香草酮的目标化合物苄基醚衍生物（ 6a-h，7a-h ）。 ）。合成化合物的结构通过各种光谱方法（FT-IR，¹H NMR、¹³ C NMR、质谱和元素分析）。然后对所有合成的化合物进行体外抗寄生虫和抗菌活性测试。生物活性测试表明，虽然只有少数化合物具有杀虫活性，但大多数具有抗菌活性。此外，使用 SwissADME 网络服务器对所有化合物的 ADME 参数、药代动力学特性和药物样性质进行了理论上的研究。最后，进行分子对接模拟以支持体外研究并评估合成化合物对 3IW2（结核分枝杆菌）的抑制作用。(Mtb) Cyp125；Pdb ID：3IW2) 受体结构。此外，根据对接结果，确定了一些对 Mtb Cyp125 具有高亲和力的化合物的可能结合位点。