Benzothiazole Derived Ether Hybrids as Potent Anti‐Thymidine Phosphorylase Agents: Synthesis, In Vitro, and Computational Investigations

作者：Muhammad Usman, Aftab Alam, Zainab Zainab, Majid Khan, Burak Tüzün, Muhammad Ayaz, Mohammed M. Alanazi, Abdul Latif, Syed Adnan Alı Shah, Humaira Hussain, Mumtaz Ali, Mumtaz Ali, Manzoor Ahmad · 发表于：Chemistry & Biodiversity · 年份：2025 · DOI：10.1002/cbdv.202403385 · 被引用次数：7 · 研究领域：Biochemical and Molecular Research、Synthesis and biological activity、Colorectal Cancer Treatments and Studies

ABSTRACT This work is based on the synthesis of new ether derivatives bearing benzothiazole (BTA) scaffold through multistep reaction process. Initially, BTA was prepared by refluxing 4‐hydroxybenzaldehyde with aminothiophenol having sodium metabisulfite in dimethylformamide (DMF); subsequently, the product was further refluxed with different substituted benzyl and alkyl bromides in acetone to get ether hybrids of BTA in good yields. Structurally, these compounds were confirmed by means of 1 H, 13 C‐NMR, and mass spectrometry and evaluated for in vitro thymidine phosphorylase (TP) inhibitory activity. In the series, seven compounds attributed excellent inhibition against TP enzyme better than the standard. Similarly, three compounds showed good activity, whereas two compounds were found inactive. Moreover, all these compounds showed no toxicity to normal human fibroblast cell line (BJ cell line). In addition, Gaussian calculations were performed on the 6‐31++g(d,p) basis set to examine the 13 synthesized compounds at the B3LYP, HF, and M062X levels. Additionally, molecular docking calculations were performed on TP enzyme proteins (PDB IDs: 4EAD, 2WK6, and 4LHM), and absorption, distribution, metabolism, excretion/toxicity (ADME/T) calculations were performed to investigate the effects and responses of these compounds in human metabolism.