Design and synthesis of 1,4-disubstituted 1,2,3-triazoles: Biological evaluation, in silico molecular docking and ADME screening

In this study, propargyl compounds were synthesized from 4-hydroxybenzaldehyde and 3-methoxy-4-hydroxybenzaldehyde (2a-2b ). As a result of click reactions of synthesized propargyl compounds (2a-b ) with organic azides (4a-4e), carbonyl compounds (5a-5h) having 1,2,3-triazole skeleton were obtained. The structures of the synthesized compounds were illuminated by FTIR, H-1/C-13 NMR spectroscopies and elemental analyses. Antioxidant and anti-cancer and alpha-amylase enzyme inhibition studies of the synIthesized compounds were carried out, and the effects of different functional groups in the compounds on the activity were investigated. When the results of the alpha-amylase enzyme inhibition studies of the synthesized compounds were compared with the reference drug acarbose (IC50: 891 mu g/mL), it was de-termined that all compounds (IC50: 165-1471 mu g/mL) showed higher activity than acarbose, except for compounds 5a and 5c . In particular, compound 5 g (IC50: 165 mu g/mL) was found to have approximately 5.5 times higher activity than acarbose. When the DPPH center dot radical scavenging studies were examined, all compounds showed a higher activity than the standard BHT and beta-carotene. According to ABTS center dot(+) radical scavenging activity results, all compounds showed more effective activity than Ascorbic acid, and Trolox used as standard. Compound 5a showed approximately the same scavenging effect with beta-carotene and BHT. Compounds were also screened for anti-cancer activities against the HeLa cell line. According to the results, 5c (IC50: 50.12 mu g/mL) and 5 h (IC50: 57.07 mu g/mL) exhibit moderate antitumor activity compared to cis-platin against the HeLa cell line. The molecules have been studied in detail for their ADME proper-ties and have not violated any drug-likeness rules. In addition, they exhibited a high oral bioavailability profile, as their BBB (Blood Brain Barrier) penetration and GI (gastrointestinal) absorption properties were favorable. Molecular docking results show that all compounds have a high affinity for the active site of alpha-amylase. (C) 2021 Elsevier B.V. All rights reserved.