Article 2023 · 36 atıf

Discovery of new 1,4-disubstituted 1,2,3-triazoles: <i>in silico</i> ADME profiling, molecular docking and biological evaluation studies

Sahin, Irfan, Cesme, Mustafa, Yuce, Neslihan, Tumer, Ferhan

Özet

In this work, eight new 1,2,3-triazoles (6a-h) were synthesized from acetylenes' "click" reaction with p-substituted azide derivatives. The structures of the compounds were characterized using standard analytical and spectroscopic methods (elemental analysis, FT-IR, H-1(C-13)NMR). The anticancer, antioxidant, alpha-amylase, ADME, molecular docking studies of synthesized triazoles were investigated. According to alpha -amylase enzyme inhibition results, all compounds except 6c (IC50: 2299 mu g/mL) were found to have a higher IC50 value than the standard drug acarbose (IC50: 891 mu g/mL). Compound 6g (IC50: 68 mu g/mL) exhibited 13 times higher activity than standard acarbose. All compounds, except 6e, have been shown to have greater DPPH radical scavenging capabilities than BHT and beta-carotene standards. According to ABTS radical scavenging studies, all compounds showed higher scavenging activity than ascorbic acid and Trolox. To determine the anticancer activity of the synthesized compounds, they were screened against the Hela cell line, and the results were compared with standard cisplatin (IC50: 16.30 mu g/mL). Compound 6a (IC50: 49.03 mu g/mL) was determined to have moderate activity relative to cisplatin. The compounds were examined comprehensively for ADME characteristics and did not violate any drug-likeness rule. ADME data showed that all physicochemical and pharmacological parameters of the compounds remained within defined limits as specified in Lipinski's rules (RO5) and put forth a high bioavailability profile. The molecular docking findings show that all molecules have a high affinity by exhibiting polar and apolar contact with essential residues in the binding pocket of alpha-amylase.

Anahtar Kelimeler

Triazoles anticancer antioxidant activity alpha-amylase inhibition in silico molecular docking ADME ANTIOXIDANT ACTIVITY ANTIMICROBIAL ACTIVITY DERIVATIVES DESIGN INHIBITORS ANTICANCER ACID

WoS Kategorileri

Biochemistry & Molecular Biology Biophysics

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Yıl: 2023
Cilt: 41
Sayı: 5
Sayfa: 1988-2001
ISSN: 0739-1102
eISSN: 1538-0254
DOI: 10.1080/07391102.2022.2025905
WoS UID: WOS:000745411200001

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