RESUMEN
BACKGROUND: Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance. METHODS: In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, and adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types while they promoted homotypic cell-cell interaction. RESULTS: These changes were reflected by the downregulation of matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited potent anti-angiogenic activity in vivo. CONCLUSION: These novel nucleobase analogs reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant CRC cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form.
Asunto(s)
Neoplasias Colorrectales , Fluorouracilo , Humanos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Metaloproteinasa 2 de la Matriz/química , Metaloproteinasa 2 de la Matriz/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Metaloproteinasa 9 de la Matriz/química , Metaloproteinasa 9 de la Matriz/metabolismoRESUMEN
A new synthetic pathway towards secosteroidal macrocycles was described via a reaction of cycloaddition as the key step. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.
Asunto(s)
Química Clic , Compuestos Macrocíclicos/síntesis química , Secoesteroides/síntesis química , Ciclización , Compuestos Macrocíclicos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Secoesteroides/químicaRESUMEN
We set out to describe an efficient and versatile method for preparing pentacyclic steroids diversely substituted at C-11 from cholic acid, via a stereoselective epoxidation and the epoxide opening as the key steps. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.
Asunto(s)
Esteroides/síntesis química , Aminas/química , Ácido Cólico/química , Compuestos Epoxi/química , Lactonas/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Estereoisomerismo , Compuestos de Sulfhidrilo/química , Sulfonas/químicaRESUMEN
An efficient synthesis of 12-hetero steroids was achieved via a Baeyer-Villiger oxidation and a photolysis as the key steps. We set out to describe in this paper the first synthesis of 12-aza steroids. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.