Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies

doi:10.1016/j.molstruc.2024.137742

IMR OpenIR

	Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies
	Khan, Maaz 1,2; Ambreen, Nida 2; Saleem, Faiza 1; Lodhi, Muhammad Arif 3; Jan, Faheem 6; Kamal, Masroor 3; Salar, Uzma 4; Taha, Muhammad 5; Khan, Khalid Mohammed 1,7,8
通讯作者	Ambreen, Nida(nidaambreen@awkum.edu.pk) ; Khan, Khalid Mohammed(khalid.khan@iccs.edu)
	2024-06-05
发表期刊	JOURNAL OF MOLECULAR STRUCTURE
ISSN	0022-2860
卷号	1305 页码:21
摘要	In an effort to develop novel enzyme inhibitors with potent activity and high selectivity, a series of nicotinonitrile derivatives was synthesized. Cyano pyridone intermediates undergo nucleophilic substitution reactions with variously substituted phenacyl halides to yield the nicotinonitriles 1-20. All nicotinonitriles exhibited moderate to excellent in vitro enzyme inhibitory activities against alpha-glucosidase, tyrosinase, and urease. Compound 1 (IC50 = 27.09 +/- 0.12 mu M) selectively displayed more significant activity than the standard acarbose (IC50 = 40.00 +/- 0.70 mu M). Compound 1 also showed good urease inhibition (IC50 = 33.04 +/- 0.70 mu M); however, it exhibited activity less than the standard acetohydroxamic acid (IC50 = 27.00 +/- 0.50 mu M). Furthermore, the most effective compound of the series against tyrosinase compared to the standard kojic acid (IC50 = 16.9 +/- 1.30 mu M) was 16 with an IC50 value of 10.55 +/- 0.08 mu M. In contrast, this compound showed no activity against alpha-glucosidase and urease. DFT calculations were carried out to analyze electronic transitions and energy levels (HOMO and LUMO) in nicotinonitrile derivatives, offering insights into their chemical reactivity and stability. Molecular docking studies and molecular electrostatic potential (MEP) revealed the interactions of the active compounds with the amino acid residues at the active sites of the enzymes, thereby shedding light on the mechanism of enzyme inhibition. Therefore, compound 1 can be further studied as a promising alpha-glucosidase and urease inhibitor, while compound 16 is an effective tyrosinase inhibitor.
关键词	Pyridine alpha -Glucosidase inhibition Tyrosinase inhibition Urease inhibition Computational studies
资助者	Pakistan Academy of Science, 3 -Constitution Avenue, Islamabad, Pakistan
DOI	10.1016/j.molstruc.2024.137742
收录类别	SCI
语种	英语
资助项目	Pakistan Academy of Science, 3 -Constitution Avenue, Islamabad, Pakistan[111]
WOS研究方向	Chemistry
WOS类目	Chemistry, Physical
WOS记录号	WOS:001199519100001
出版者	ELSEVIER
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/185471
专题	中国科学院金属研究所
通讯作者	Ambreen, Nida; Khan, Khalid Mohammed
作者单位	1.Univ Karachi, Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan 2.Abdul Wali Khan Univ, Dept Chem, Mardan 23200, Pakistan 3.Abdul Wali Khan Univ, Dept Biochem, Mardan 23200, Pakistan 4.Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan 5.Imam Abdulrahman Bin Faisal Univ, Inst Res & Med Consultat IRMC, Dept Clin Pharm, POB 31441, Dammam, Saudi Arabia 6.Chinese Acad Sci, Inst Met Res, Shenyang Natl Lab Mat Sci, Shenyang, Liaoning, Peoples R China 7.Pakistan Acad Sci, 3 Constitut Ave,G-5-2, Islamabad 44000, Pakistan 8.Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan
推荐引用方式 GB/T 7714	Khan, Maaz,Ambreen, Nida,Saleem, Faiza,et al. Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies[J]. JOURNAL OF MOLECULAR STRUCTURE,2024,1305:21.
APA	Khan, Maaz.,Ambreen, Nida.,Saleem, Faiza.,Lodhi, Muhammad Arif.,Jan, Faheem.,...&Khan, Khalid Mohammed.(2024).Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies.JOURNAL OF MOLECULAR STRUCTURE,1305,21.
MLA	Khan, Maaz,et al."Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies".JOURNAL OF MOLECULAR STRUCTURE 1305(2024):21.