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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: NEW JOURNAL OF CHEMISTRY; v. 44, n. 29, p. 12440-12451, AUG 7 2020.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 17/06146-8 - Development of nanocarriers based on dendrimers and polymer nanoparticles for selective delivery of goniothalamin, piplartine and Monastrol
• Grantee: Carolyne Brustolin Braga
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/13104-5 - Planning and synthesis of inhibitors based on biological targets: the case of neglected kinases
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/02093-0 - Development of new nanomaterials for nanomedicine applications
• Grantee: Cátia Cristina Capêlo Ornelas Megiatto
• Support Opportunities: Regular Research Grants