ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Novel oxazole derivatives as anti-diabetic agents along with in silico modeling: a critical analysis of recent trends and finding

Shoaib Khan, Tayyiaba Iqbal, Wajid Rehman, Mujaddad Ur Rehman, Rafaqat Hussain, Aisha Bibi, and Ayed A. Dera

Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad, Pakistan

E-mail: shoaibkhanswati@gmail.com

Received: 1 February 2025  Accepted: 9 September 2025

Abstract:

Oxazole derived amide-based azomethines derivatives were synthesized through an efficient and facile route in this research work. By comparing with reference drug acarbose having IC₅₀ = 7.50 ± 0.20 µM for α-amylase and 8.10 ± 0.40 µM for α-glucosidase, it was revealed that all the novel synthesized analogues exhibit varying degree of inhibition against both enzymes. The remarkably good (top ranked) anti-diabetic competitor against both enzymes was found with IC₅₀ = 5.30 ± 0.20 µM 5.80 ± 0.10 µM) against α-amylase α-glucosidase, respectively. Other potent analogs of the series having IC₅₀ (6.90 ± 0.40, 7.20 ± 0.10 µM), (7.60 ± 0.20, 8.10 ± 0.20 µM) and (7.80 ± 0.20, 9.10 ± 0.10 µM) also displayed excellent biological potential by engaging the active site of targeted enzymes through different interactions. The impact of substitutions on the drug profile of newly designed candidates was determined through the structure activity relationship. In silico molecular docking analysis was also conducted to predict that how the target proteins (enzyme) interact with the ligands by visualizing the 2D and 3D mode of binding interactions. The drug effectiveness of these analogues was assessed through ADMET analysis. By applying spectroscopic techniques ¹HNMR, ¹³CNMR and HREI-MS the structural skeleton of newly designed analogues was identified. This study presents novel therapeutic agents for the future treatment of diabetes mellitus.

Graphical abstract

Keywords: Diabetes mellitus; Oxazole; Molecular docking; ADMET

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04380-2

Chemical Papers 79 (12) 9125–9140 (2025)