当前位置: X-MOL 学术Chem. Biodivers. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Synthesis of Palladium-Catalysed C−C Bond Forming 5-Chloro Quinolines via Suzuki-Miyaura Coupling; Anti-Pancreatic Cancer Screening on PANC-1 Cell Lines
Chemistry & Biodiversity ( IF 2.9 ) Pub Date : 2022-11-27 , DOI: 10.1002/cbdv.202200622
Abdul Rahman 1 , Nippu Belur Ningegowda 1 , Manjunatha Kammathalli Siddappa 1 , Meghana Pargi 2 , Honnenahally Malleshappa Kumaraswamy 2 , Nayak Devappa Satyanarayan 1 , Rajeshwara Achur 3
Affiliation  

Pancreatic cancer is the most severe among other cancers due to its late detection and less chance of survivability. Heterocycles are proven ring systems in the treatment of various cancers and this is due to the presence of two biodynamic molecules combined, which have a greater synergistic efficacy in many anticancer drugs. Quinoline and pyridine ring systems are brought together to obtain greater potency and this is achieved by coupling both using Pd-catalyst, and in the present investigation, Suzuki-Miyaura coupling (SMC) reactions are adopted to generate potent molecular entities. Pancreatic cancer is difficult to treat due to overexpression of the VEGFR2 protein. VEGFR2 is targeted to design the molecules of quinoline-coupled pyridine moieties and is docked to evaluate the protein-ligand interaction at the binding site. The binding affinity of conjugates revealed the potency and capability of ligands to inhibit the VEGFR2 pathway. The in-silico ADMET properties determined their inherent pharmacokinetic feasibility. The synthesized conjugates have been evaluated by MTT assay against the human pancreatic cancer cell lines (PANC-1). Among the series, compounds 5d, 5e, and 5h exhibited a greater inhibitory activity against the cell lines with an IC50 value of 82.32±1.38, 54.74±1.18 and 80.35±1.68 μM. In the present exploration, 5e exhibited greater inhibitory activity and it could be a promising lead for the development of new chemotherapeutics against pancreatic cancer.

中文翻译:

Suzuki-Miyaura 偶联钯催化 C−C 键形成 5-氯喹啉的合成;PANC-1 细胞系的抗胰腺癌筛选

胰腺癌是其他癌症中最严重的,因为它发现较晚且生存机会较少。杂环化合物在治疗各种癌症方面已被证明是环状系统,这是由于存在两种生物动力分子组合,它们在许多抗癌药物中具有更大的协同功效。喹啉和吡啶环系统结合在一起以获得更大的效力,这是通过使用 Pd 催化剂偶联来实现的,在本研究中,采用铃木-宫浦偶联 (SMC) 反应来产生有效的分子实体。由于 VEGFR2 蛋白的过度表达,胰腺癌难以治疗。VEGFR2 的目标是设计喹啉偶联的吡啶部分的分子,并被对接以评估结合位点的蛋白质-配体相互作用。缀合物的结合亲和力揭示了配体抑制 VEGFR2 通路的效力和能力。这in-silico ADMET 特性决定了它们固有的药代动力学可行性。已通过针对人胰腺癌细胞系 (PANC-1) 的 MTT 测定评估了合成的缀合物。其中,化合物5d5e5h对细胞系表现出更强的抑制活性,IC 50值为82.32±1.38、54.74±1.18和80.35±1.68 μM。在目前的探索中,5e表现出更强的抑制活性,它可能成为开发新的胰腺癌化疗药物的有前途的线索。
更新日期:2022-11-27
down
wechat
bug