Bis-indole based triazine derivatives: Synthesis, characterization, in vitro β-glucuronidase anti-cancer and anti-bacterial evaluation along with in silico molecular docking and ADME analysis

• Published in: Arabian journal of chemistry 2023-08, Vol.16 (8), p.104970, Article 104970
• Main Authors: Khan, Shoaib, Rehman, Wajid, Rahim, Fazal, Hussain, Rafaqat, Obaidullah, Ahmad J., Faris Alotaibi, Hadil, Alanazi, Mohammed M., Usman Khan, Muhammad, Khan, Yousaf
• Format: Article
• Language: English
• Subjects: Indole; Molecular docking & ADME; SAR; Triazine synthesis; β-Glucuronidase
• ISSN: 1878-5352; 1878-5379
• DOI: 10.1016/j.arabjc.2023.104970

The present work described the synthetic procedure adopted for the synthesis of bis-indole-based triazine derivatives via a series of reactions. All the compounds were synthesized through a stepwise reaction. After being confirmation through thin-layer chromatography (TLC) these compounds were characterized through various spectroscopic techniques including 1HNMR, 13CNMR and HREI-MS and evaluated against beta-glucuronidase in the presence of standard drug D-saccharic acid 1,4 lactone (IC50 = 31.2 ± 1.0 µM). Most of the synthesized derivatives were found with better to good inhibitory potentials (IC50 = 5.30 ± 2.0 µM to 33.10 ± 1.0 µM). SAR explains better results of analogs due to the presence of varied substituents on the aromatic rings. In this regard, the excellent potential was shown by analogs 1, 3, 6, 8 and 9 with IC50 = 5.30 ± 2.0, 7.10 ± 4.0, 6.10 ± 3.0, 8.40 ± 1.0 and 7.20 ± 3.0 µM respectively). In addition, all the synthesized analogs were evaluated for anti-cancer and anti-bacterial (E. coli) activities in which the targeted compounds were found with significant potentials in the presence of standard drugs Tetrandrineb (IC50 = 1.37 ± 0.10 µM) and streptomycin respectively. These derivatives were further subjected to molecular docking studies in order to investigate better binding sites with distance. Additionally, ADME properties for the synthesized compounds were also explored the drug like properties of the synthesized compounds.