Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase

Shoaib Khan; Shahid Iqbal; Muhammad Taha; Fazal Rahim; Mazloom Shah; Hayat Ullah; Ali Bahadur; Hamad Alrbyawi; Ayed A Dera; Mohammed Issa Alahmdi; Rami Adel Pashameah; Eman Alzahrani; Abd-ElAziem Farouk

doi:10.3390/molecules27217368

Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase

Molecules. 2022 Oct 29;27(21):7368. doi: 10.3390/molecules27217368.

Authors

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
² Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad 46000, Pakistan.
³ Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrah-Man Bin Faisal University, Dammam 34212, Saudi Arabia.
⁴ Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan.
⁵ Department of Chemistry, University of Okara, Okara 56300, Pakistan.
⁶ Department of Chemistry, College of Science and Technology, Wenzhou-Kean University, Wenzhou 325060, China.
⁷ Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Medina 42353, Saudi Arabia.
⁸ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61413, Saudi Arabia.
⁹ Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
¹⁰ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia.
¹¹ Department of Chemistry, College of Science, Taif University, Taif 21944, Saudi Arabia.
¹² Department of Biotechnology, College of Science, Taif University, Taif 21944, Saudi Arabia.

Abstract

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1-16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including ¹H, ¹³CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure-activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.

Keywords: AchE and BuChE inhibitors; SAR; indole; molecular docking; thiadiazole analogs.

MeSH terms

Acetylcholinesterase* / metabolism
Cholinesterase Inhibitors / chemistry
Indoles / pharmacology
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Thiadiazoles* / chemistry
Thiadiazoles* / pharmacology

Substances

Acetylcholinesterase
Cholinesterase Inhibitors
Thiadiazoles
Indoles

Abstract

MeSH terms

Substances

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