RESUMO
Multicomponent reactions (MCRs) are a valuable tool in diversity-oriented synthesis. Its application to privileged structures is gaining relevance in the fields of organic and medicinal chemistry. Isatin, due to its unique reactivity, can undergo different MCRs, affording multiple interesting scaffolds, namely oxindole-derivatives (including spirooxindoles, bis-oxindoles and 3,3-disubstituted oxindoles) and even, under certain conditions, ring-opening reactions occur that leads to other heterocyclic compounds. Over the past few years, new methodologies have been described for the application of this important and easily available starting material in MCRs. In this review, we explore these novelties, displaying them according to the structure of the final products obtained.
RESUMO
In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents the core for a wide range of bioactive naturally isolated products (such as Strychnofoline and spirotryprostatins A and B) and synthetic compounds. Interestingly, no much attention has been paid to develop spirooxindole derivatives with dual antioxidant and anticancer activities. In this context, a series of spirooxindoles 6a-p was examined for their anticancer effect towards HepG2 hepatocellular carcinoma and PC-3 prostate cancer cell lines. Spirooxindole 6a was found to be an efficient anti-proliferative agent towards both HepG2 and PC-3 cells (IC50 = 6.9 and 11.8 µM, respectively). Afterwards, spirooxindole 6a was assessed for its apoptosis induction potential in HepG2 cells, where its pro-apoptotic impact was approved via the significant elevation in the Bax/Bcl-2 ratio and the expression levels of caspase-3.
Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Oxindóis/farmacologia , Compostos de Espiro/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/antagonistas & inibidores , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estrutura Molecular , Oxindóis/síntese química , Oxindóis/química , Células PC-3 , Picratos/antagonistas & inibidores , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Spirocompounds constitute an important class of organic frameworks enveloping numerous pharmacological activities, among them, the promising anticancer potential of spirocompounds have enthused medicinal chemists to explore new spiro derivatives with significantly improved pharmacodynamic and pharmacokinetic profile along with their mechanism of action. The current review intends to provide a sketch of the anticancer activity of various spirocompounds like spirooxindole, spiroisoxazole, spiroindole etc, from the past five years unfolding various aspects of pharmacological activities and their structure-activity relationships (SARs). This literature analysis may provide future direction for the efficient design of novel spiromolecules with enhanced safety and efficacy.