Synthesis and Evaluation of Some Novel 1,3-Dimethylbarbituric Acid Derivatives as Potent Anti-Urease Agents: Comprehension through <i>In Vitro</i>, Molecular Docking, and DFT Investigations

doi:10.1134/S1068162024050042

IMR OpenIR

	*Synthesis and Evaluation of Some Novel 1,3-Dimethylbarbituric Acid Derivatives as Potent Anti-Urease Agents: Comprehension through In Vitro, Molecular Docking, and DFT Investigations*
	Gul, Misbah 1; Jan, Faheem 2,3; Alam, Aftab 4; Ahmad, Imtiaz 6; Habib, Uzma 5; Khan, Momin 1; Alasmari, Abdullah F.7; Alasmari, Fawaz 7; Khan, Ajmal 8; Al-Harrasi, Ahmed 8
通讯作者	Khan, Momin(mominkhan@awkum.edu.pk) ; Al-Harrasi, Ahmed(aharrasi@unizwa.edu.om)
	2024-10-01
发表期刊	RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
ISSN	1068-1620
卷号	50 期号:5 页码:1609-1626
摘要	Objective: To synthesize bis-Schiff bases bearing thiobarbituric acid and to screen their anti-urease inhibitory potential. Methods: In this study, 1,3-dimethylbarbituric acid derivatives were synthesized by a four-step process. Using K2CO3, 2,4-dihydroxy benzaldehyde and chloro ethyl acetate were esterified in DMF in the first step under reflux condition. The reaction was then carried out by combining the esterified aldehyde with 1,3-dimethylbarbituric acid at room temperature for about an 1 h. Hydrazine hydrate was then mixed with compound (II) in ethanol solvent with acetic acid acting as catalyst. Finally, substituted aromatic aldehydes were treated with bis-hydrazide (III) using ethanol and acetic acid as a catalyst. Results: The newly synthesized compounds were screened for their urease inhibition (in vitro). Four analogs, including (IIIj) (IC50 = 15.22 +/- 0.49 mu M), (IIIg) (IC50 = 16.05 +/- 0.16 mu M), (IIIa) (IC50 = 16.29 +/- 0.73 mu M), and (IIIb) (IC50 = 21.17 +/- 0.21 mu M) were found most powerful inhibitors than standard thiourea (IC50 = 22.80 +/- 2.20 mu M). The urease inhibition was also seen in compound (IIIi), (IIIc), (IIIh), (IIIe), (IIId), and (IIIf) however it was less from standard. The structure stability and chemical reactivity of the compounds were checked by density functional theory (DFT) method. Furthermore, the molecular docking simulation was performed to check the protein (urease) and ligand interactions and binding affinities by using AutoDock Vina. Conclusions: The synthesized derivatives attributed temendous potential against urease enzyme. Compound (IIIj) was found as the most potent anti-urease agent. Additional research including taxicological and in vivo is necessary to know the safety, effectivness and mechanism of action of these potent molecules.
关键词	barbituric acid bis-hydrazide-hydrazone urease inhibition NMR spectroscopy molecular docking study
资助者	Saud University, Riyadh, Saudi Arabia
DOI	10.1134/S1068162024050042
收录类别	SCI
语种	英语
资助项目	Saud University, Riyadh, Saudi Arabia[RSP2024R235]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:001337204100033
出版者	MAIK NAUKA/INTERPERIODICA/SPRINGER
引用统计	被引频次：1[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/321006/190790
专题	中国科学院金属研究所
通讯作者	Khan, Momin; Al-Harrasi, Ahmed
作者单位	1.Abdul Wali Khan Univ, Dept Chem, Mardan 23200, Pakistan 2.Chinese Acad Sci, Inst Met Res, Shenyang Natl Lab Mat Sci, Shenyang 110016, Liaoning, Peoples R China 3.Univ Sci & Technol China, Sch Mat Sci & Engn, Shenyang 110016, Liaoning, Peoples R China 4.Univ Malakand, Dept Chem, Dir Lower 18800, Kpk, Pakistan 5.Natl Univ Sci & Technol NUST, Sch Interdisciplinary Engn & Sci SINES, Sect H 12, Islamabad 44000, Pakistan 6.Univ Fed Pelotas, Programa Pos Graduacao Bioquim & Bioprospeccao, Lab Neuroquim Inflamacao & Canc, Campus Univ Capao Leao s-n, BR-96010900 Pelotas, RS, Brazil 7.King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia 8.Univ Nizwa, Nat & Med Sci Res Ctr, Birkat Al Mauz 616, Nizwa, Oman
推荐引用方式 GB/T 7714	Gul, Misbah,Jan, Faheem,Alam, Aftab,et al. Synthesis and Evaluation of Some Novel 1,3-Dimethylbarbituric Acid Derivatives as Potent Anti-Urease Agents: Comprehension through In Vitro, Molecular Docking, and DFT Investigations[J]. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY,2024,50(5):1609-1626.
APA	Gul, Misbah.,Jan, Faheem.,Alam, Aftab.,Ahmad, Imtiaz.,Habib, Uzma.,...&Al-Harrasi, Ahmed.(2024).Synthesis and Evaluation of Some Novel 1,3-Dimethylbarbituric Acid Derivatives as Potent Anti-Urease Agents: Comprehension through In Vitro, Molecular Docking, and DFT Investigations.RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY,50(5),1609-1626.
MLA	Gul, Misbah,et al."Synthesis and Evaluation of Some Novel 1,3-Dimethylbarbituric Acid Derivatives as Potent Anti-Urease Agents: Comprehension through In Vitro, Molecular Docking, and DFT Investigations".RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 50.5(2024):1609-1626.