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
Affiliations
Shoaib Khan
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Shahid Iqbal
Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad 46000, Pakistan
Muhammad Taha
Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrah-Man Bin Faisal University, Dammam 34212, Saudi Arabia
Fazal Rahim
Department of Chemistry, Hazara University, Mansehra 21120, Pakistan
Mazloom Shah
Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan
Hayat Ullah
Department of Chemistry, University of Okara, Okara 56300, Pakistan
Ali Bahadur
Department of Chemistry, College of Science and Technology, Wenzhou-Kean University, Wenzhou 325060, China
Hamad Alrbyawi
Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Medina 42353, Saudi Arabia
Ayed A. Dera
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61413, Saudi Arabia
Mohammed Issa Alahmdi
Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Rami Adel Pashameah
Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia
Eman Alzahrani
Department of Chemistry, College of Science, Taif University, Taif 21944, Saudi Arabia
Abd-ElAziem Farouk
Department of Biotechnology, College of Science, Taif University, Taif 21944, Saudi Arabia
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.
