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

被引：43

作者：

Khan, Shoaib ^{[1
]}

Iqbal, Shahid ^{[2
]}

Taha, Muhammad ^{[3
]}

Rahim, Fazal ^{[1
]}

Shah, Mazloom ^{[4
]}

Ullah, Hayat ^{[5
]}

Bahadur, Ali ^{[6
]}

Alrbyawi, Hamad ^{[7
]}

Dera, Ayed A. ^{[8
]}

Alahmdi, Mohammed Issa ^{[9
]}

Pashameah, Rami Adel ^{[10
]}

Alzahrani, Eman ^{[11
]}

Farouk, Abd-ElAziem ^{[12
]}

机构：

[1] Hazara Univ, Dept Chem, Mansehra 21120, Pakistan

[2] Natl Univ Sci & Technol NUST, Sch Nat Sci SNS, Dept Chem, H-12, Islamabad 46000, Pakistan

[3] Imam Abdulrah Man Bin Faisal Univ, Inst Res & Med Consultat IRMC, Dept Clin Pharm, Dammam 34212, Saudi Arabia

[4] Abbottabad Univ Sci & Technol AUST, Dept Chem, Abbottabad 22500, Pakistan

[5] Univ Okara, Dept Chem, Okara 56300, Pakistan

[6] Wenzhou Kean Univ, Coll Sci & Technol, Dept Chem, Wenzhou 325060, Peoples R China

[7] Taibah Univ, Coll Pharm, Pharmaceut & Pharmaceut Technol Dept, Medina 42353, Saudi Arabia

[8] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha 61413, Saudi Arabia

[9] Univ Tabuk, Fac Sci, Dept Chem, Tabuk 71491, Saudi Arabia

[10] Umm Al Qura Univ, Fac Appl Sci, Dept Chem, Mecca 24230, Saudi Arabia

[11] Taif Univ, Coll Sci, Dept Chem, Taif 21944, Saudi Arabia

[12] Taif Univ, Coll Sci, Dept Biotechnol, Taif 21944, Saudi Arabia

来源：

MOLECULES | 2022年 / 27卷 / 21期

关键词：

indole; thiadiazole analogs; SAR; AchE and BuChE inhibitors; molecular docking; ALZHEIMERS-DISEASE; BUTYRYLCHOLINESTERASE; DESIGN; TARGET; AGENTS;

D O I：

10.3390/molecules27217368

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 H-1, (CNMR)-C-13 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.

引用

页数：12

共 38 条

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