Indole bearing thiadiazole analogs: synthesis, β-glucuronidase inhibition and molecular docking study

Noor Barak Almandil; Muhammad Taha; Mohammed Gollapalli; Fazal Rahim; Mohamed Ibrahim; Ashik Mosaddik; El Hassane Anouar

doi:10.1186/s13065-019-0522-x

Indole bearing thiadiazole analogs: synthesis, β-glucuronidase inhibition and molecular docking study

BMC Chem. 2019 Feb 4;13(1):14. doi: 10.1186/s13065-019-0522-x. eCollection 2019 Dec.

Authors

Affiliations

¹ 1Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia.
² 3Department of Computer Information Systems, College of Computer Science & Information Technology, Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia.
³ 2Department of Chemistry, Hazara University, Mansehra, 21300 Khyber Pakhtunkhwa Pakistan.
⁴ 4Department of Chemistry, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, P.O. Box 83, Al-Kharj, 11942 Saudi Arabia.

^# Contributed equally.

Abstract

Indole based thiadiazole derivatives (1-22) have synthesized, characterized by NMR and HREI-MS and evaluated for β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC₅₀ values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC₅₀ value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC₅₀ value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.

Keywords: Indole; Molecular docking; SAR; Synthesis; Thiadiazole; β-Glucuronidases.