Novel 1,2,3-Triazole Linked Chromene Hybrids: Microwave-Assisted Synthesis, Cytotoxic Activity, α-amylase Inhibitory Potential, Molecular Docking Analysis, and In-silico ADMET Profiling

• Published in: Chemistry Africa Vol. 7; no. 6; pp. 3129 - 3148
• Main Authors: Hajlaoui, Amel, Chortani, Sarra, Morjen, Maram, Lazrag, Houda, Kibou, Zahira, Choukchou-braham, Noureddine, Srairi-Abid, Najet, Marrakchi, Naziha, Jannet, Hichem Ben, Romdhane, Anis
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2024
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; Organometallic Chemistry; Original Article; Anti-α-amylase; 1,3-Dipolar cycloaddition; Chromene-based triazoles; Kinetics; Molecular docking; Melanoma
• ISSN: 2522-5758; 2522-5766
• DOI: 10.1007/s42250-024-01024-y

This paper presents an efficient microwave-assisted synthesis of novel hybrid 1,4-disubstituted triazole derivatives under copper(I) catalyst. The formulas of the obtained products were determined based on spectroscopic data (HRMS, NMR). The compounds were assessed in vitro for their pharmacological activities and found that four derivatives (2, 4h, 4j, and 4k) were active against the development of murine (B16F10) and human (IGR-39) melanoma cell lines. Our results also indicated that the synthesized hybrids exhibited considerable anti-α-amylase activity. Conjugate 4b, with 2,4,5-triCl-Ph moiety, proved to be the most potent agent in the series (IC 50  = 9.13 ± 1.37 μM), even compared to the positive control (acarbose, IC 50  = 21.84 ± 1.06 μM). The kinetic analysis showed that some inhibitors are competitive, while others are non-competitive. The molecular docking study showed that the compounds bind to a variety of putative targeted proteins, such as: B-Raf Kinase V600E (PDB-3OG7), EGFR (PDB-1M17), Human MEK1 kinase (PDB-3WIG), and Pancreatic α-amylase (PDB-3BAJ). A variety of physicochemical, pharmacokinetic, and toxicological properties of the prepared analogs indicated that they were within the desired limits, revealing a good ADMET profile. Graphical abstract