Exploring 1,3,4-Oxadiazole derivatives of 3,4-Dihydroxyphenylacetic acid as potent α-glucosidase inhibitors: Synthesis, structure-activity relationship, molecular docking, and DFT studies

doi:10.1016/j.molstruc.2024.141211

IMR OpenIR

	Exploring 1,3,4-Oxadiazole derivatives of 3,4-Dihydroxyphenylacetic acid as potent α-glucosidase inhibitors: Synthesis, structure-activity relationship, molecular docking, and DFT studies
	Khan, Hammad 1; Jan, Faheem 2; Aqsa 1; Ullah, Qudrat 1; Alasmari, Abdullah F.3; Alasmari, Fawaz 3; Khan, Ajmal 4,5; Ullah, Saeed 4; Alam, Aftab 6; Al-Harrasi, Ahmed 4; Khan, Momin 7; Ali, Shaukat 1
通讯作者	Al-Harrasi, Ahmed(aharrasi@unizwa.edu.om) ; Khan, Momin(mominkhan@awkum.edu.pk) ; Ali, Shaukat(drshaukatali@uop.edu.pk)
	2025-04-15
发表期刊	JOURNAL OF MOLECULAR STRUCTURE
ISSN	0022-2860
卷号	1327 页码:11
摘要	The current work aims to synthesize some new 1,3,4-oxadiazole derivatives bearing 3,4-dihydroxyphenyl acetic acid scaffold as a novel class of alpha-glucosidase inhibitors. A series of novel 1,3,4-oxadiazole derivatives (1-10) of 3,4-dihydroxyphenylacetic acid were synthesized in a series of multi-step reactions. All the synthesized compounds were obtained in good yields (70-85 %), and their structures were determined using 1H-NMR, 13C-NMR and HR-ESI-MS spectroscopy. All derivatives showed excellent to moderate alpha-glucosidase inhibition. Specifically compounds, 2 (IC50 = 17.24 +/- 0.49 mu M), 7 (IC50 = 18.10 +/- 0.72 mu M), 3 (IC50 = 19.34 +/- 0.45 mu M), 5 (IC50 = 20.38 +/- 0.74 mu M), 6 (IC50 = 22.59 +/- 0.74 mu M), 9 (IC50 = 23.18 +/- 1.10 mu M), 4 (IC50 = 24.10 +/- 0.59 mu M), and 1 (IC50 = 25.62 +/- 0.69 mu M) exhibited outstanding inhibition compared to the standard acarbose (IC50 = 873.34 +/- 1.67 mu M). The novelty of this work lies in the effective derivation of 1,3,4-oxadiazoles, posing a new support for alpha-glucosidase inhibitors with encouraging activity. Furthermore, the docking study was carried out to find out the interactions between the active site of the enzyme and the synthesized compounds. Density functional theory (DFT) calculations at B3LYP/6-311++G(d,p) were utilized to ensure the structure stability. Reduced density gradient (RDG) and DFT-D3 methods were used to account for intramolecular interaction. Additionally, the chemical nature of all the compounds was identified using the TD-DFT at the CAM-B3LYP/ 6-311++G(d,p) method. The results of this work highlight the potential of these compounds as powerful candidates for further development of current alpha-glucosidase inhibitors.
关键词	Oxadiazole & Acy 3,4-dihydroxyphenylacetic acid Spectroscopy Molecular docking and DFT -glucosidase
资助者	King Saud University, and Riyadh, Saudi Arabia
DOI	10.1016/j.molstruc.2024.141211
收录类别	SCI
语种	英语
资助项目	King Saud University, and Riyadh, Saudi Arabia[RSP2025R335]
WOS研究方向	Chemistry
WOS类目	Chemistry, Physical
WOS记录号	WOS:001420289000001
出版者	ELSEVIER
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/179947
专题	中国科学院金属研究所
通讯作者	Al-Harrasi, Ahmed; Khan, Momin; Ali, Shaukat
作者单位	1.Univ Peshawar, Inst Chem Sci, Organ Synth & Catalysis Res Lab, Peshawar 25120, Khyber Pakhtunk, Pakistan 2.Chinese Acad Sci, Inst Met Res, Shenyang Natl Lab Mat Sci, Shenyang 110016, Liaoning, Peoples R China 3.King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia 4.Univ Nizwa, Nat & Med Sci Res Ctr, POB 33, Nizwa 616, Oman 5.Korea Univ, Coll Engn, Dept Chem & Biol Engn, Seoul 02841, South Korea 6.Univ Malakand, Dept Chem, Chakdara 18800, Lower Dir, Pakistan 7.Abdul Wali Khan Univ, Dept Chem, Mardan 23200, Pakistan
推荐引用方式 GB/T 7714	Khan, Hammad,Jan, Faheem,Aqsa,et al. Exploring 1,3,4-Oxadiazole derivatives of 3,4-Dihydroxyphenylacetic acid as potent α-glucosidase inhibitors: Synthesis, structure-activity relationship, molecular docking, and DFT studies[J]. JOURNAL OF MOLECULAR STRUCTURE,2025,1327:11.
APA	Khan, Hammad.,Jan, Faheem.,Aqsa.,Ullah, Qudrat.,Alasmari, Abdullah F..,...&Ali, Shaukat.(2025).Exploring 1,3,4-Oxadiazole derivatives of 3,4-Dihydroxyphenylacetic acid as potent α-glucosidase inhibitors: Synthesis, structure-activity relationship, molecular docking, and DFT studies.JOURNAL OF MOLECULAR STRUCTURE,1327,11.
MLA	Khan, Hammad,et al."Exploring 1,3,4-Oxadiazole derivatives of 3,4-Dihydroxyphenylacetic acid as potent α-glucosidase inhibitors: Synthesis, structure-activity relationship, molecular docking, and DFT studies".JOURNAL OF MOLECULAR STRUCTURE 1327(2025):11.