Nicotinonitriles as potential inhibitors of α-glucosidase, tyrosinase, and urease enzymes: Synthesis, characterization, in vitro, and in silico studies
文献类型：期刊论文
| 作者 | Khan, Maaz1,2; Ambreen, Nida2; Saleem, Faiza1; Lodhi, Muhammad Arif3; Jan, Faheem6; Kamal, Masroor3; Salar, Uzma4; Taha, Muhammad5; Khan, Khalid Mohammed1,7,8 |
| 刊名 | JOURNAL OF MOLECULAR STRUCTURE
 |
| 出版日期 | 2024-06-05 |
| 卷号 | 1305页码:21 |
| 关键词 | Pyridine alpha -Glucosidase inhibition Tyrosinase inhibition Urease inhibition Computational studies |
| ISSN号 | 0022-2860 |
| DOI | 10.1016/j.molstruc.2024.137742 |
| 通讯作者 | Ambreen, Nida(nidaambreen@awkum.edu.pk) ; Khan, Khalid Mohammed(khalid.khan@iccs.edu) |
| 英文摘要 | 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. |
| 资助项目 | Pakistan Academy of Science, 3 -Constitution Avenue, Islamabad, Pakistan[111] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001199519100001 |
| 出版者 | ELSEVIER |
| 资助机构 | Pakistan Academy of Science, 3 -Constitution Avenue, Islamabad, Pakistan |
| 源URL |  |
| 专题 | 金属研究所_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. |
入库方式： OAI收割
来源：金属研究所
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