Synthesis, Anti-enzymatic Appraisal, In Silico, and SAR Analysis of 5-Aryl/Heteroaryl-2,2-dimethyl-1,3-dioxane-4,6-dione Derivatives

被引:0
|
作者
Khatoon, Saira [1 ]
Mehfooz, Haroon [1 ]
Shehzadi, Syeda Aaliya [2 ]
Saeed, Aamer [1 ]
Kalsoom, Saima [3 ]
Channar, Pervaiz Ali [4 ]
Ismail, Hammad [5 ]
Rauf, Abdul [6 ]
Naveed, Sana [2 ]
Taslimi, Parham [7 ]
El-Seedi, Hesham [8 ]
机构
[1] Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan
[2] Int Islamic Univ, Sulaiman Bin Abdullah Aba Al Khail Ctr Interdiscip, SA CIRBS, Islamabad 44000, Pakistan
[3] PMAS Arid Agr Univ, Dept Chem, Rawalpindi 46020, Pakistan
[4] Dawood Univ Engn & Technol, Fac Informat Sci & Humanities, Dept Basic Sci & Humanities, Karachi 74800, Pakistan
[5] Univ Gujrat, Dept Biochem & Mol Biol, Gujrat 50700, Pakistan
[6] Islamia Univ Bahawalpur, Dept Chem, Bahawalpur 63100, Pakistan
[7] Bartin Univ, Fac Sci, Dept Biotechnol, TR-74100 Bartin, Turkiye
[8] Islamic Univ Madinah, Fac Sci, Dept Chem, Al Madinah Al Munawwarah 42351, Saudi Arabia
来源
CHEMISTRYSELECT | 2025年 / 10卷 / 06期
关键词
Chymotrypsin inhibitors; Meldrum's acid; Molecular docking; SAR; Urease inhibitors; MELDRUMS ACID-DERIVATIVES; JACK BEAN UREASE; ALPHA-CHYMOTRYPSIN; ORGANIC-SYNTHESIS; KINETIC MECHANISM; INHIBITORS; NOROVIRUSES; PROTEASES; ALDEHYDES; PLATFORM;
D O I
10.1002/slct.202404787
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A sequence of new 5-aryl/heteroaryl-2,2-dimethyl-1,3-dioxane-4,6-dione derivatives were synthesized by condensing Meldrum's acid and triethyl orthoformate with differently substituted aromatic and heteroaromatic amines in good to excellent yields. The chemical structures were characterized by spectroscopic techniques and the synthesized entities were evaluated for chymotrypsin and urease inhibition. Interestingly, among the synthesized derivatives, compound containing 5-nitropyridin-2-yl ring exhibited dual inhibition activities with IC50 value (8.67 +/- 0.1) close to the control (Chymostatin:8.24 +/- 0.11) against chymotrypsin; and (29.21 +/- 0.98) close to the control (Thiourea:21.25 +/- 0.15) urease in mu M concentration. Further, molecular docking analysis was performed on the 3D crystal structure of Jack bean urease protein and a serine proteinase alpha-chymotrypsin with synthesized ligands, to observe the binding interactions. All the synthesized compounds docked well into the active sites of the proteins, the most active compound showed H-bonding interaction with amino acid HIS A 594 residue through carbonyl oxygen of dioxane ring and CME A 592 through oxygen of nitro group against 3La4 urease protein, while against chymotrypsin, it revealed the hydrogen bonding between amino acids: SER C 217, GLY C 216, and SER C 190. The role of pharmacophore was evaluated using the diverse substituents on aromatic/heteroaromatic rings, and on the basis of that SAR was developed.
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页数:16
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