Identification of novel oxadiazole-based benzothiazole derivatives as potent inhibitors of α-glucosidase and urease: Synthesis, in vitro bio-evaluation and their in silico molecular docking study

• Published in: Journal of Saudi Chemical Society Vol. 27; no. 4; p. 101682
• Main Authors: Khan, Yousaf, Maalik, Aneela, Rehman, Wajid, Hussain, Rafaqat, Khan, Shoaib, Alanazi, Mohammed M., Asiri, Hanadi H, Iqbal, Shahid
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2023; Elsevier
• Subjects: Benzothiazole; Molecular docking; Oxadiazole; SAR; Synthesis; Urease; α-glucosidase; α-glucosidase; Synthesis; SAR; Benzothiazole; Oxadiazole; Urease; Molecular docking
• ISSN: 1319-6103
• DOI: 10.1016/j.jscs.2023.101682

This research work represents a synthetic approach for the development of hybrids derivatives of oxadiazole-based benzothiazole (1–17) and diversity in derivatives was achieved using variety of aryl ring of S-substituted benzothiazole to see the effect on the biological activities. All the synthesized derivatives were evaluated for their in vitro α-glucosidase and urease inhibitory potential. The α-glucosidase and urease inhibition profile of the new derivatives represents moderate to good inhibitory potential with IC50 values ranging from 4.60 ± 1.20 µM to 48.40 ± 7.70 µM (α-glucosidase) and 8.90 ± 2.80 to 57.30 ± 7.70 µM (urease) respectively. The results were compared to standard acarbose (38.60 ± 4.50 µM) and thiourea (58.70 ± 6.80 µM) drugs respectively. Among the synthesized series, the analogs 1 having IC50 values of and 4.60 ± 1.20 (α-glucosidase), 8.90 ± 2.80 (urease) and 2 with IC50 values of 5.60 ± 1.60 (α-glucosidase) and 10.90 ± 2.10(urease) were found to be significantly active against targeted α-glucosidase and urease enzymes. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, 1H- and 13C- NMR spectroscopy. The molecular docking studies of the synthesized derivatives showed good correlations with the experimental findings. The binding modes of active compounds and their interactions with active site residues revealed them as possible anti-diabetics and anti-urease leads. The degree of activity and docking studies displayed by the novel innovative structural hybrids of oxadiazole-based benzothiazole moieties make these compounds new active leads and promising candidates for the development of anti-diabetics and anti-urease agents.