Benzylpyrazolyl naphthoquinones as potential VEGFR-2, GPCR and PPAR inhibitors: Synthesis, anti-cancer evaluation, molecular docking and DFT studies

被引:4
|
作者
Patil, Pradnya [1 ]
Patil, Pruthanka [2 ]
Dandge, Padma [3 ]
Bansode, Prakash [4 ]
Kumbhar, Bajarang [2 ]
Chandane, Wilson [1 ]
Rathod, Sanket [5 ]
Choudhari, Prafulla [5 ]
Khot, Suraj [1 ]
Valekar, Navanath [1 ]
Pore, Dattaprasad [1 ]
Rashinkar, Gajanan [1 ]
机构
[1] Shivaji Univ, Dept Chem, Kolhapur 416004, India
[2] Deemed Univ, Dept Biol Sci, Sunandan Divatia Sch Sci, SVKMs Narsee Monjee Inst Management Studies NMIMS, Mumbai 400056, India
[3] Shivaji Univ, Dept Biochem, Kolhapur 416004, India
[4] Sangola Coll, Dept Chem, Sangola 413307, India
[5] Bharati Vidyapeeth Coll Pharm, Dept Pharmaceut Chem, Kolhapur 416013, India
关键词
Anti-cancer activity; Benzylpyrazolyl naphthoquinones; Bronsted acidic ionic liquid; Molecular docking; ANTIOXIDANT; DERIVATIVES; DESIGN; TOOL;
D O I
10.1016/j.molstruc.2023.137202
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The present study reports the synthesis of benzylpyrazolyl naphthoquinones using nano-Fe3O4 supported Bronsted acidic ionic liquid ([nano-Fe3O4@BenzImi]SO3H) as magnetically retrievable solid acid catalyst. In vitro anti-cancer activity of the synthesized benzylpyrazolyl naphthoquinones have been evaluated against breast cancer cell line (MCF-7) and liver cancer cell line (HepG2). Compound 4h was found to be the most active compounds with IC50 values 0.0436 +/- 0.31 mu M against MCF 7 cell line whereas compound 4e was displayed highest activity with IC50 values 0.0314 +/- 0.16 mu M against HepG2 cell line as compared to the standard 5-fluorouracil (0.0384 +/- 0.10 and 0.0330 +/- 0.09 mu M). Furthermore, in silico bioactivity studies revealed that the compounds have significant interactions with the drug targets. The molecular docking studies revealed that the compounds have significant binding affinity with potential receptors such as vascular endothelial growth factor receptor (VEGFR-2), G-protein coupled receptor (GPCR) and peroxisome proliferator-activated receptors (PPAR). The compound 4g has strong hydrogen bond interaction with VEGFR-2 as well as the lowest binding energy (-9.3 kcal/mol-1), similarly, 4c has strong hydrogen bond interaction with in GPCR as well as the lowest binding energy (-7.8 kcal/mol-1) whereas 4a and 4e show strong hydrogen bond interaction with in PPAR as well as lowest binding energy (-10.1 kcal/mol- 1 and -10.1 kcal/mol- 1) as compared to other compounds. The docking studies revealed that these compounds gets stabilized via hydrogen bonding interactions, van der Waals contacts and electrostatic interactions which were further supported through estimation of HOMO-LUMO energies, ionization potential, electron affinities, dipole moment etc. using density functional theory (DFT) analysis. The work highlights biological significance of benzylpyrazolyl naphthoquinones as a potential anti-cancer reagent.
引用
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页数:13
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