Botany and Microbiology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Research Department of Chemistry, Nehru Memorial College (Affiliated with the Bharathidasan University), Puthanampatti, Tiruchirappalli District, Tamil Nadu, South India.
Drug Des Devel Ther. 2020 Oct 23;14:4477-4492. doi: 10.2147/DDDT.S270896. eCollection 2020.
A new series of tetrazole derivatives, which are renowned antimicrobials possessing a five-membered aromatic heterocyclic group, are synthesized herein and subjected to antimicrobial and cytotoxicity screening.
The tetrazole derivatives were synthesized via ultrasonication using Mannich base condensation. Structural verification of the products was performed using IR, H NMR, and C NMR spectroscopy, as well as mass spectroscopic and elemental analyses. The compounds were then screened for antimicrobial and cytotoxic activity against HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cell lines. Inter- and intra-molecular binding interactions were determined using molecular docking studies. The exact binding mode between the most active tetrazole derivatives (ie, 1b, 2a, and 2b) and the proteins (ie, 4OR7, 1AI9, and 4FM9) was established using Autodock Vina 1.1.2 software and compared to the binding mode of the reference compounds (ie, cefazolin, clotrimazole, and fluorouracil).
Compound 1b was extremely active against relative to the positive control cefazolin. Compounds 1b and 1e were active against and compared to the positive control clotrimazole in antifungal screening. The HepG2 (liver) and MCF-7 (breast) cancer cell lines were particularly susceptible to the synthesized compounds. Compared to the control compound fluorouracil, 2a and 2b were extremely active against all three cancer cell lines. Molecular docking studies showed that 2b exhibited higher binding affinity (-7.8 kcal/mol) to the 4OR7 protein than the control cefazolin (-7.2 kcal/mol).
Generally, 1b, 2a, and 2b exhibited impressive inhibitory capabilities in antibacterial, antifungal, and cytotoxic screenings relative to the reference compounds. The results of the molecular docking studies and both the microbial and anticancer screenings indicate that these novel derivatives could be developed into potential therapeutic agents for medical applications.
本文合成了一系列新的噻唑衍生物，这些化合物是具有五元芳香杂环基团的著名抗菌药物，并对其进行了抗菌和细胞毒性筛选。
通过曼尼希碱缩合反应，使用超声波技术合成了噻唑衍生物。使用红外光谱（IR）、核磁共振氢谱（H NMR）和碳谱（C NMR）光谱、质谱和元素分析对产物进行了结构验证。然后，对这些化合物进行了抗 HepG2（肝）、MCF-7（乳腺）和 HeLa（宫颈）细胞系的抗菌和细胞毒性活性筛选。使用分子对接研究确定了化合物之间和化合物与蛋白质之间的相互作用。使用 Autodock Vina 1.1.2 软件确定了最活跃的噻唑衍生物（即 1b、2a 和 2b）与蛋白质（即 4OR7、1AI9 和 4FM9）之间的精确结合模式，并将其与参考化合物（即头孢唑林、克霉唑和氟尿嘧啶）的结合模式进行了比较。
化合物 1b 对 表现出极高的活性，优于阳性对照头孢唑林。在抗真菌筛选中，化合物 1b 和 1e 对 表现出活性，优于阳性对照克霉唑。合成的化合物对 HepG2（肝）和 MCF-7（乳腺）癌细胞系特别敏感。与对照化合物氟尿嘧啶相比，2a 和 2b 对所有三种癌细胞系均表现出极高的活性。分子对接研究表明，2b 对 4OR7 蛋白的结合亲和力（-7.8 kcal/mol）高于对照头孢唑林（-7.2 kcal/mol）。
总体而言，与参考化合物相比，1b、2a 和 2b 在抗菌、抗真菌和细胞毒性筛选中表现出令人印象深刻的抑制能力。分子对接研究以及微生物和抗癌筛选的结果表明，这些新型衍生物可能被开发为用于医学应用的潜在治疗药物。
