Evaluation of 2,3-Dihydro-1,5-benzothiazepine Derivatives as Potential Tyrosinase Inhibitors: In Vitro and In Silico Studies

被引:14
作者
Al-Rooqi, Munirah M. [1 ]
Sadiq, Amina [2 ]
Obaid, Rami J. [1 ]
Ashraf, Zaman [3 ]
Nazir, Yasir [3 ,4 ]
Jassas, Rabab S. [5 ]
Naeem, Nafeesa [6 ]
Alsharif, Meshari A. [1 ]
Shah, Syed Wadud Ali [7 ]
Moussa, Ziad [8 ]
Mughal, Ehsan Ullah [6 ]
Farghaly, Abdel-Rahman [9 ]
Ahmed, Saleh A. [1 ]
机构
[1] Umm Al Qura Univ, Fac Appl Sci, Dept Chem, Mecca 21955, Saudi Arabia
[2] Govt Coll Women Univ, Dept Chem, Sialkot 51300, Pakistan
[3] Allama Iqbal Open Univ, Dept Chem, Islamabad 44000, Pakistan
[4] Univ Sialkot, Dept Chem, Sialkot 51300, Pakistan
[5] Umm Al Qura Univ, Jamoum Univ Coll, Dept Chem, Mecca 21955, Saudi Arabia
[6] Univ Gujrat, Dept Chem, Gujrat 50700, Pakistan
[7] Univ Malakand, Dept Pharm, Chakdara Dir 18000, Khyber Pakhtunk, Pakistan
[8] United Arab Emirates Univ, Coll Sci, Dept Chem, Abu Dhabi, U Arab Emirates
[9] Jazan Univ, Coll Sci, Dept Chem, Jazan 114, Saudi Arabia
关键词
BIOLOGICAL EVALUATION; MOLECULAR DOCKING; CHEMISTRY; 1,5-BENZOTHIAZEPINE; ANALOGS;
D O I
10.1021/acsomega.3c01566
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Benzothiazepines are pharmacologically active compounds, frequently utilized as a precursor for acquiring versatile molecules with several bioactivities including anti-inflammatory, tumor, antimicrobial, and antitubercular. In this study, the 2,4diphenyl-2,3-dihydro-1,5-benzothiazepine scaffold was selected for their in vitro, docking, and druglikeness studies to evaluate their inhibitory potential against mushroom tyrosinase. All synthesized analogues, 1-14, exhibited moderate to good IC50 values ranging from 1.21 to 70.65 mu M. The synthesized benzothiazepine derivatives were potent tyrosinase inhibitors, which outperformed the reference kojic acid (IC50 = 16.69 mu M). The kinetic analysis revealed that compound 2 (2-(3,4-dimethoxyphenyl)-4-(p-tolyl)2,3-dihydrobenzo[b][1,4]thiazepine) was a mixed-type tyrosinase inhibitor with a Ki value of 1.01 mu M. Molecular modeling studies against tyrosinase protein (PDB ID: 2Y9X) were conducted to recognize the binding modes of these analogues. The utilization of molecular dynamic (MD) simulations enabled the assessment of the protein-ligand complex's dynamic behavior, stability, and binding affinity for the compounds. These simulations ultimately led to the identification of compound 2 as a potential inhibitor of tyrosinase. Additionally, a druglikeness study was conducted, which supported the promising potential of the new analogues as novel antityrosinase agents. The in silico studies were consistent with the in vitro results, showing that these ligands had good binding scores against tyrosinase and interacted with the core residues of the target protein. Gaussian 09 was used for the geometry optimization of all complexes.
引用
收藏
页码:17195 / 17208
页数:14
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