Exploring 3-hydroxyflavone scaffolds as mushroom tyrosinase inhibitors: synthesis, X-ray crystallography, antimicrobial, fluorescence behaviour, structure-activity relationship and molecular modelling studies

被引：37

作者：

Ashraf, Jamshaid ^{[1
]}

Mughal, Ehsan Ullah ^{[1
]}

Sadiq, Amina ^{[2
]}

Bibi, Maryam ^{[1
]}

Naeem, Nafeesa ^{[1
]}

Ali, Anser ^{[3
]}

Massadaq, Anam ^{[3
]}

Fatima, Nighat ^{[4
]}

Javid, Asif ^{[1
]}

Zafar, Muhammad Naveed ^{[5
]}

Khan, Bilal Ahmad ^{[6
]}

Nazar, Muhammad Faizan ^{[1
]}

Mumtaz, Amara ^{[7
]}

Tahir, Muhammad Nawaz ^{[8
]}

Mirzaei, Masoud ^{[9
]}

机构：

[1] Univ Gujrat, Dept Chem, Gujrat 50700, Pakistan

[2] Govt Coll Women Univ, Dept Chem, Sialkot, Pakistan

[3] Mirpur Univ Sci & Technol, Dept Zool, Mirpur 10250, Ajk, Pakistan

[4] COMSATS Univ Islamabad, Dept Pharm, Abbotabad, Pakistan

[5] Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan

[6] Univ Azad Jammu & Kashmir, Dept Chem, Muzaffarabad, Pakistan

[7] COMSATS Univ Islamabad, Dept Chem, Abbottabad, Pakistan

[8] Univ Sargodha, Dept Phys, Sargodha, Pakistan

[9] Ferdowsi Univ Mashhad, Fac Sci, Dept Chem, Mashhad, Razavi Khorasan, Iran

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2021年 / 39卷 / 18期

关键词：

3-hydroxyflavones; Algar-Flynn-Oyamada reaction; antibacterial; antifungal; tyrosinase enzyme inhibition; molecular docking studies; BIOLOGICAL EVALUATION; CRYSTAL-STRUCTURE; PLANT FLAVONOIDS; IN-VITRO; KINASE; ANTIOXIDANT; DERIVATIVES; DOCKING; MELANIN; ABSORPTION;

D O I：

10.1080/07391102.2020.1805364

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To explore new scaffolds as tyrosinase enzyme inhibitors remain an interesting goal in the drug discovery and development. In due course and our approach to synthesize bioactive compounds, a series of varyingly substituted 3-hydroxyflavone derivatives (1-23) were synthesized in one-pot reaction and screened forin vitroagainst mushroom tyrosinase enzyme. The structures of newly synthesized compounds were unambiguously corroborated by usual spectroscopic techniques (FTIR, UV-Vis,H-1-,C-13-NMR) and mass spectrometry (EI-MS). The structure of compound15was also characterized by X-ray diffraction analysis. Furthermore, the synthesized compounds (1-23) were evaluated for their antimicrobial potential. Biological studies exhibit pretty good activity against most of the bacterial-fungal strains and their activity is comparable to those of commercially available antibioticsi.e.Cefixime and Clotrimazole. Amongst the series, the compounds2, 4, 5, 6, 7, 10, 11, 14and22exhibited excellent inhibitory activity against tyrosinase, even better than standard compound. Remarkably, the compound2(IC50= 0.280 +/- 0.010 mu g/ml) was found almost sixfold and derivative5(IC50= 0.230 +/- 0.020 mu g/ml) about sevenfold more active as compared to standard Kojic acid (IC50=1.79 +/- 0.6 mu g/ml). Moreover, these synthetic compounds (1-23) displayed good to moderate activities against tested bacterial and fungal strains. Their emission behavior was also investigated in order to know their potential as fluorescent probes. The molecular modelling simulations were also performed to explore their binding interactions with active sites of the tyrosinase enzyme. Limited structure-activity relationship was established to design and develop new tyrosinase inhibitors by employing 2-arylchromone as a structural core in the future. Communicated by Ramaswamy H. Sarma

引用

页码：7107 / 7122

页数：16

共 77 条

[11] Comparative evaluation of microleakage in class II cavities restored with Ceram X and Filtek P-90: An in vitro study [J].