Synthesis, confirmations and biological evaluation of acid substituted Schiff base Derivatives: Unraveling insight through SAR, DFT, ADMET and molecular docking

• Published in: Results in Chemistry 2024-10, Vol.11, p.101744, Article 101744
• Main Authors: Amjid, Zaineb, Khan, Shoaib, Iqbal, Tayyiaba, Hussain, Rafaqat, Zafar Ali, Hafeeza, Shoaib, Khurram, Khan, Yousaf, Ullah, Hayat, Arshad, Sabeen, Iqbal, Rashid, Ullah, Riaz, Ali, Essam A.
• Format: Article
• Language: English
• Subjects: ADME; Diabetes; Molecular Docking; Schiff Base
• ISSN: 2211-7156; 2211-7156
• DOI: 10.1016/j.rechem.2024.101744

[Display omitted] •This study presents a novel route for the synthesis of different acid Substituted Schiff Base Derivatives.•These derivatives were biological investigated for their anti-diabetic potential.•The structural confirmation of the synthesized compounds was achieved via spectroscopic analysis.•These derivatives were subjected to in silico molecular docking study to gain insight into the binding interactions with target enzymes.•Reactivity of the potent compounds was also analyzed via Density Functional Theory (DFT).•These derivatives were also investigated for their pharmacokinetic properties through ADME analysis to study their drug likeness attributes. In this study we have adopted a new synthetic route for different substituted Schiff base derivatives (1–10) and examined their anti-diabetic potential. All these compounds exhibited a varied range against α-amylase and α-glucosidase with antidiabetic potential. Analog (6) with triflouro methyl substituent, present on the para position of the ring was emerged as most potent compound. Acarbose was used as reference drug with IC50 = 6.80 ± 0.40 μM and 7.20 ± 0.70 μM for α-amylase and α-glucosidase, respectively. Furthermore, antibacterial and antifungal activity of these compounds was also evaluated against E. coli and A. alternate in the presence of marketed drug Terbinafine and Streptomycin. Binding modalities of synthesized compounds with the receptor residues of target enzymes were explored by in silico docking. Additionally, ADME analysis and DFT were also conducted to assess the drug-like characteristics and electronic properties of the potent derivatives. The synthesized compounds were confirmed through spectroscopic techniques such as 13C NMR, 1H NMR and HREI-Mass spectrometry.