Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations

doi:10.1016/j.molstruc.2024.138459

IMR OpenIR

	Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations
	Jan, Faheem 1,2; Idris, Sana 3; Waheed, Mahnoor 3; Alam, Aftab 4; Alasmari, Abdullah F.5; Alasmari, Fawaz 5; Khan, Momin 3
通讯作者	Alam, Aftab(aaswat117@gmail.com) ; Khan, Momin(mominkhan@awkum.edu.pk)
	2024-09-05
发表期刊	JOURNAL OF MOLECULAR STRUCTURE
ISSN	0022-2860
卷号	1311 页码:15
摘要	A library of thiosemicarbazones derivatives have been synthesized by multi step reactions, characterized and screened for their in vitro alpha-amylase and alpha-glucosidase inhibitory actions. Among them, three compounds including 4b (IC50 = 3.18 +/- 1.72 and 2.11 +/- 1.29 mu M), 4a (IC50 = 5.16 +/- 1.12 and 7.23 +/- 0.11 mu M), and 4 g (IC50 = 7.13 +/- 1.21 and 9.53 +/- 0.29 mu M) are found as potential dual inhibitors of alpha-amylase and alpha-glucosidase enzymes, powerfull than the standard acarbose drug (IC50 = 21.55 +/- 1.31 and 16.65 +/- 0.07 mu M). In addition, compounds 4c, 4f, 4 h, 4d, and 4e indicated significant to less inhibitory potential. Molecular docking was performed to know the binding affinities and various interactions between the synthesized compounds and targeted proteins. For the docking analysis, the protein structure of alpha-amylase was taken from the Protein Data Bank (PDB) with the code 3BAJ, derived from Homo sapiens. Meanwhile, the protein structure of alpha-glucosidase was obtained from Beta vulgaris with the PDB code 3W37. The chemical nature of the product compounds was identified using the density functional theory (DFT) method, and the calculations were performed using the B3LYP/6-311++G(d,p) method. Intramolecular interactions were explored using DFT-d3 and Reduced Density Gradient (RDG) analysis. Furthermore, the chemical nature of all the compounds was identified using TD-DFT at the CAM-B3LYP/6-311++G(d,p) method. Among the synthesized compounds, 4a, 4b, and 4g show similar inhibition activities with targeted proteins. Similar activities have been confirmed using the TD-DFT method. The energy gap between the highest occupied molecular orbitals and lowest unoccopied was found as, 6.07, 6.08, and 6.07 eV, respectively. The similarty in energy gap indicated these compounds have similiar reactivity nature.
关键词	Thiosemicarbazones Hydrazone-Schiff bases Diabetes mellitus alpha-glucosidase alpha-amylase DFT and molecular docking
资助者	King Saud University, Riyadh, Saudi Arabia
DOI	10.1016/j.molstruc.2024.138459
收录类别	SCI
语种	英语
资助项目	King Saud University, Riyadh, Saudi Arabia[RSP2024R335]
WOS研究方向	Chemistry
WOS类目	Chemistry, Physical
WOS记录号	WOS:001237365300001
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/321006/186758
专题	中国科学院金属研究所
通讯作者	Alam, Aftab; Khan, Momin
作者单位	1.Chinese Acad Sci, Shenyang Natl Lab Mat Sci, Inst Met Res, Shenyang 110016, Liaoning, Peoples R China 2.Univ Sci & Technol China, Sch Mat Sci & Engn, Shenyang 110016, Liaoning, Peoples R China 3.Abdul Wali Khan Univ, Dept Chem, Mardan 23200, Pakistan 4.Univ Malakand, Dept Chem, Dir 18800, Khyber Pakhtunk, Pakistan 5.King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia
推荐引用方式 GB/T 7714	Jan, Faheem,Idris, Sana,Waheed, Mahnoor,et al. Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations[J]. JOURNAL OF MOLECULAR STRUCTURE,2024,1311:15.
APA	Jan, Faheem.,Idris, Sana.,Waheed, Mahnoor.,Alam, Aftab.,Alasmari, Abdullah F..,...&Khan, Momin.(2024).Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations.JOURNAL OF MOLECULAR STRUCTURE,1311,15.
MLA	Jan, Faheem,et al."Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations".JOURNAL OF MOLECULAR STRUCTURE 1311(2024):15.