Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents

被引：15

作者：

Aktas, Derya Anil ^{[1
]}

Akinalp, Gokcen ^{[2
]}

Sanli, Fatma ^{[3
,4
]}

Yucel, Mehmet Ali ^{[5
,6
]}

Gambacorta, Nicola ^{[5
]}

Nicolotti, Orazio ^{[5
]}

Karatas, Omer Faruk ^{[3
,4
]}

Algul, Oztekin ^{[6
]}

Burmaoglu, Serdar ^{[2
]}

机构：

[1] Ataturk Univ, Erzurum Vocat High Sch, Dept Chem & Chem Proc Technol, TR-25240 Erzurum, Turkey

[2] Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkey

[3] Erzurum Tech Univ, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey

[4] Erzurum Tech Univ, High Technol Applicat & Res Ctr, Mol Canc Biol Lab, Erzurum, Turkey

[5] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Via E Orabona 4, I-70125 Bari, Italy

[6] Mersin Univ, Fac Pharm, Dept Pharmaceut Chem, TR-33169 Mersin, Turkey

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 19期

关键词：

Synthesis; Isoxazole; Anticancer agent; Molecular modeling; Proliferation; PROSTATE-CANCER; CYTOCHROME-P450; 1B1; SUPPRESSION; INHIBITION; EXPRESSION; APOPTOSIS;

D O I：

10.1016/j.bmcl.2020.127427

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The present study was carried out in the attempt to synthesize a new class of potential anticancer agents comprising eleven compounds (24-34) sharing the 3,5-diarylisoxazole as a core. The chemical structure of the new synthesized compounds was established by IR, H-1 NMR, C-13 NMR and elemental analysis. Their biological potential towards prostate cancer was evaluated by using cancer PC3 cells and non-tumorigenic PNT1a cells. Interestingly, compound 26 distinguished from others with a quite high selectivity value that is comparable to 5-FU. The binding mode of 26 towards Ribosomal protein S6 kinase beta-1 (S6K1) was investigated at a molecular level of detail by employing docking simulations based on GLIDE standard precision as well as MM-GBSA calculations.

引用

页数：4

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