PDF(Pubmed)
Abstract：
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (-9.9; -70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π-cation bond with Phe92, and a salt bridge with the polar residue Asp27.
摘要：
设计了一系列新型的咖啡酸1,2,4-三唑类似物，合成，characterized,并评估其抑制DHFR的能力，以及它们的抗癌和抗菌性能。对DHFR进行了分子对接分析，利用PDBID1U72和2W9S，旨在设计抗癌和抗菌药物，分别。在所有合成的衍生物中，化合物CTh7表现出作为DHFR抑制剂的最高效力，IC50值为0.15μM。此外,它表现出显著的细胞毒性，IC50值为8.53µM。CTh7化合物的分子对接分析表明，它与智人DHFR的关键残基如目标蛋白结合位点内的Glu30，Phe34，Tyr121，Ile16，Val115和Phe31形成强相互作用，并显示出优异的对接分数和结合能（-9.9;-70.38kcal/mol）。此外,合成的化合物进行了抗菌性能的筛选，揭示了对细菌菌株的显着抗菌潜力和对真菌菌株的中等影响。具体来说,化合物CTh3对金黄色葡萄球菌表现出显著的抗菌效果(MIC=5µM)。同样，化合物CTh4对大肠杆菌和铜绿假单胞菌均具有显著的抗菌活性,每个MIC值为5µM。对最具活性的抗微生物化合物CTh3的对接分析表明，它与Thr121和Asn18形成氢键，与Phe92形成π阳离子键，并与极性残基Asp27形成盐桥。
