Synthesis, in vitro biological assessment, and molecular docking study of benzimidazole-based thiadiazole derivatives as dual inhibitors of α-amylase and α-glucosidase

Shoaib Khan; Shahid Iqbal; Muhammad Taha; Rafaqat Hussain; Fazal Rahim; Mazloom Shah; Nasser S Awwad; Hala A Ibrahium; Mohammed Issa Alahmdi; Ayed A Dera; Hayat Ullah; Ali Bahadur; Samar O Aljazzar; Eslam B Elkaeed; Muhammad Rauf

doi:10.3389/fchem.2023.1125915

Synthesis, in vitro biological assessment, and molecular docking study of benzimidazole-based thiadiazole derivatives as dual inhibitors of α-amylase and α-glucosidase

Front Chem. 2023 May 5:11:1125915. doi: 10.3389/fchem.2023.1125915. eCollection 2023.

Authors

Shoaib Khan¹, Shahid Iqbal², Muhammad Taha³, Rafaqat Hussain¹, Fazal Rahim¹, Mazloom Shah⁴, Nasser S Awwad⁵, Hala A Ibrahium^{6

7}, Mohammed Issa Alahmdi⁸, Ayed A Dera⁹, Hayat Ullah¹⁰, Ali Bahadur¹¹, Samar O Aljazzar¹², Eslam B Elkaeed¹³, Muhammad Rauf¹⁴

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra, Pakistan.
² Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), Islamabad, Pakistan.
³ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
⁴ Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad, Pakistan.
⁵ Department of Chemistry, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Biology, Nuclear Materials Authority, El Maadi, Egypt.
⁷ Department of Semi Pilot Plant, Nuclear Materials Authority, El Maadi, Egypt.
⁸ Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.
⁹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
¹⁰ Department of Chemistry, University of Okara, Okara, Punjab, Pakistan.
¹¹ Department of Chemistry, College of Science and Technology, Wenzhou-Kean University, Wenzhou, China.
¹² Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
¹³ Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia.
¹⁴ Department of Chemistry, School of Science, University of Management and Technology, Lahore, Pakistan.

Abstract

The clinical significance of benzimidazole-containing drugs has increased in the current study, making them more effective scaffolds. These moieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including ¹H-NMR, ¹³C-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against α-amylase and α-glucosidase, all derivatives (1-17) were assessed for their biological potential. Compared to the reference drug acarbose (IC₅₀ = 8.24 ± 0.08 µM), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC₅₀ = 1.10 ± 0.10 & 2.10 ± 0.10 µM, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of α-amylase and α-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances had with the various amino acid residues of the targeted enzymes for this purpose.

Keywords: SAR and molecular docking; benzimidazole; synthesis; thiadiazol; α-amylase; α-glucosidase.

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for supporting this work through research groups program under grant number RGP.2/273/44. This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R134), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. The authors extend their appreciation to the Research Center at AlMaarefa University for funding this work.