Hybrid 3,4-dihydropyrimidin-2-(thi)ones as dual-functional bioactive molecules: fluorescent probes and cytotoxic agents to cancer cells

被引：29

作者：

de Souza, Vanessa P. ^{[1
]}

Santos, Fabiano S. ^{[2
]}

Rodembusch, Fabiano S. ^{[2
]}

Braga, Carolyne B. ^{[3
]}

Ornelas, Catia ^{[3
]}

Pilli, Ronaldo A. ^{[3
]}

Russowsky, Dennis ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Inst Quim, Lab Sinteses Organ, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Inst Quim, Grp Pesquisa Fotoquim Organ Aplicada, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS, Brazil

[3] Univ Estadual Campinas, Inst Quim, BR-13084971 Campinas, SP, Brazil

来源：

NEW JOURNAL OF CHEMISTRY | 2020年 / 44卷 / 29期

基金：

巴西圣保罗研究基金会;

关键词：

INTRAMOLECULAR PROTON-TRANSFER; ONE-POT SYNTHESIS; ORGANIC NANOPARTICLES; RAFT POLYMERIZATION; BIGINELLI REACTION; DERIVATIVES; ESIPT; WATER; DYES; PHOTOPHYSICS;

D O I：

10.1039/d0nj01368d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of new hybrid fluorescent Biginelli compounds, including a Monastrol derivative, were designed and synthesized with good yields. The photophysical studies revealed dual fluorescence emission, attributed to excited enol forms (E*) and tautomeric (K*) species, respectively, due to the ESIPT mechanism. The cytotoxic activity of all compounds was evaluated against MCF-7, Caco-2 and PC3 cancer cell lines and PNT2 normal prostate cells. The fluorescent Monastrol derivative8fwas the most active with cytotoxic activity very similar to cisplatin, whereas derivative8cwas the most selective towards the PC3 prostate cancer cells. The confocal laser scanning microscopy images of PC3 and MCF-7 cancer cell lines were acquired after incubation of the fluorescent Biginelli hybrids8cand8f, respectively, demonstrating efficient cellular uptake of both compounds and strong fluorescence within the intracellular medium. These results show that the new hybrid 3,4-dihydropyrimidin-2-(thi)ones are dual-function bioactive compounds that act both as fluorescent probes and antineoplastic agents.

引用

页码：12440 / 12451

页数：12

共 64 条

[1] Synthesis and fluorescence properties of benzoxazole-1,4-dihydropyridine dyads achieved by a multicomponent reaction [J].

Affeldt, Ricardo Ferreira ;

de Amorim Borges, Antonio Cesar ;

Russowsky, Dennis ;

Rodembusch, Fabiano Severo .

NEW JOURNAL OF CHEMISTRY, 2014, 38 (09) :4607-4614

[2] Photophysical properties of a series of 4-aryl substituted 1,4-dihydropyridines [J].

Affeldt, Ricardo Ferreira ;

Iglesias, Rodrigo Sebastian ;

Rodembusch, Fabiano Severo ;

Russowsky, Dennis .

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, 2012, 25 (09) :769-777

[3] Synthesis and Fluorescence Properties of new Monastrol Analogs Conjugated Fluorescent Coumarin Scaffolds [J].

Al-Masoudi, Najim A. ;

Al-Salihi, Niran J. ;

Marich, Yossra A. ;

Markus, Timo .

JOURNAL OF FLUORESCENCE, 2016, 26 (01) :31-35

[4] Heteropolyacid-Containing Ionic Liquid-Catalyzed Multicomponent Synthesis of Bridgehead Nitrogen Heterocycles: Mechanisms and Mitochondrial Staining [J].

Alvim, Haline G. O. ;

Correa, Jose R. ;

Assumpcao, Jose A. F. ;

da Silva, Wender A. ;

Rodrigues, Marcelo O. ;

de Macedo, Julio L. ;

Fioramonte, Mariana ;

Gozzo, Fabio C. ;

Gatto, Claudia C. ;

Neto, Brenno A. D. .

JOURNAL OF ORGANIC CHEMISTRY, 2018, 83 (07) :4044-4053

[5] Diversity-Oriented Synthesis of Highly Fluorescent Fused Isoquinolines for Specific Subcellular Localization [J].

Amador-Sanchez, Yoarhy A. ;

Aguilar-Granda, Andrs ;

Flores-Cruz, Ricardo ;

Gonzalez-Calderon, Davir ;

Orta, Cynthia ;

Rodriguez-Molina, Braulio ;

Jimenez-Sanchez, Arturo ;

Miranda, Luis D. .

JOURNAL OF ORGANIC CHEMISTRY, 2020, 85 (02) :633-649

[6] 2-(4-ALKYLAMIDO-2-HYDROXYPHENYL)BENZ-X-AZOLES AS INTERMEDIATES FOR THE SYNTHESIS OF DYES [J].

BARNI, E ;

SAVARINO, P ;

MARZONA, M ;

PIVA, M .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1983, 20 (06) :1517-1521

[7]

Biginelli P., 1893, GAZZ CHIM ITAL, V23, P360

[8] Identification and characterization of 4-aryl-3,4-dihydropyrimidin2(1H)-ones as inhibitors of the fatty acid transporter FATP4 [J].

Blackburn, C ;

Guan, B ;

Brown, J ;

Cullis, C ;

Condon, SM ;

Jenkins, TJ ;

Peluso, S ;

Ye, YC ;

Gimeno, RE ;

Punreddy, S ;

Sun, Y ;

Wu, H ;

Hubbard, B ;

Kaushik, V ;

Tummino, P ;

Sanchetti, P ;

Sun, DY ;

Daniels, T ;

Tozzo, E ;

Balani, SK ;

Raman, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (13) :3504-3509

[9] Combinatorial Discovery of Fluorescent Pharmacophores by Multicomponent Reactions in Droplet Arrays [J].

Burchak, Olga N. ;

Mugherli, Laurent ;

Ostuni, Mariano ;

Lacapere, Jean Jacques ;

Balakirev, Maxim Y. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (26) :10058-10061

[10]

Campo LF, 2000, MACROMOL RAPID COMM, V21, P832, DOI 10.1002/1521-3927(20000801)21:12<832::AID-MARC832>3.0.CO

← 1 2 3 4 5 6 7 →