Spectrofluorimetric and Computational Investigation of New Phthalimide Derivatives towards Human Neutrophil Elastase Inhibition and Antiproliferative Activity

被引：5

作者：

Donarska, Beata ^{[1
]}

Switalska, Marta ^{[2
]}

Wietrzyk, Joanna ^{[2
]}

Plazinski, Wojciech ^{[3
,4
]}

Laczkowski, Krzysztof Z. Z. ^{[1
]}

机构：

[1] Nicolaus Copernicus Univ, Coll Med, Fac Pharm, Dept Chem Technol & Pharmaceut, Jurasza 2, PL-85089 Bydgoszcz, Poland

[2] Polish Acad Sci, Hirszfeld Inst Immunol & Expt Therapy, Rudolfa Weigla 12, PL-53114 Wroclaw, Poland

[3] Polish Acad Sci, Jerzy Haber Inst Catalysis & Surface Chem, Niezapominajek 8, PL-30239 Krakow, Poland

[4] Med Univ Lublin, Dept Biopharm, Chodzki 4a, PL-20093 Lublin, Poland

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 01期

关键词：

spectrofluorimetric method; human neutrophil elastase; antiproliferative activity; phthalimide; thiazole; BIOLOGICAL EVALUATION; ANALOGS; DESIGN; THIAZOLES; OPTIMIZATION; LEUKEMIA; GROWTH; POTENT; MODEL; ACID;

D O I：

10.3390/ijms24010110

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：

Herein, nine phthalimide-based thiazoles (4a-4i) were synthesized and investigated as new human neutrophil elastase (HNE) inhibitors using spectrofluorimetric and computational methods. The most active compounds containing 4-trifluoromethyl (4c), 4-naphthyl (4e) and 2,4,6-trichloro (4h) substituents in the phenyl ring exhibited high HNE inhibitory activity with IC50 values of 12.98-16.62 mu M. Additionally, compound 4c exhibited mixed mechanism of action. Computational investigation provided a consistent picture of the ligand-receptor pattern of inter-actions, common for the whole considered group of compounds. Moreover, compounds 4b, 4c, 4d and 4f showed high antiproliferative activity against human cancer cells lines MV4-11, and A549 with IC50 values of 8.21 to 25.57 mu M. Additionally, compound 4g showed high activity against MDA-MB-231 and UMUC-3 with IC50 values of 9.66 and 19.81 mu M, respectively. Spectrophotometric analysis showed that the most active compound 4c demonstrated high stability under physiological conditions.

引用

页数：17

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