RESUMO
In this article, we report the synthesis and cytotoxicity evaluation of novel indole-carrying semicarbazide derivatives (IS1-IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H-indole-2-carbohydrazide that was in-house synthesized from 1H-indole-2-carboxylic acid. Following structural characterization by 1 H-NMR, 13 C-NMR, and HR-MS, IS1-IS15 were investigated for their cytotoxic activity against human breast cancer cell lines, MCF-7 and MDA-MB-231. According to the data obtained from the MTT assay, phenyl ring with a lipophilic group at its para-position and alkyl moiety were preferential substituents on the indole-semicarbazide scaffold for antiproliferative activity. The effect of IS12 (N-(4-chloro-3-(trifluoromethyl)phenyl)-2-(1H-indole-2-carbonyl)hydrazine-1-carboxamide), the compound that demonstrated remarkable antiproliferative activity on both cell lines, was also evaluated on the apoptotic pathway. Moreover, the calculation of critical descriptors constituting drug-likeness confirmed the position of the selected compounds in the anticancer drug development process. Finally, molecular docking studies suggested the inhibition of tubulin polymerization as the potential activity mechanism of this class of molecules.
Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Neoplasias da Mama/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Antineoplásicos/química , Linhagem Celular , Indóis/química , Semicarbazidas/farmacologia , Estrutura Molecular , Linhagem Celular TumoralRESUMO
Bastimolide B is a polyhydroxy macrolide isolated from marine cyanobacteria displaying antimalarial activity. It features a dense array of hydroxylated stereogenic centers with 1,5-relationships along a hydrocarbon chain. These 1,5-polyols represent a particularly challenging motif for synthesis, as the remote position of the stereocenters hampers stereocontrol. Herein, we present a strategy for 1,5-polyol stereocontrolled synthesis based on iterative boronic ester homologation with enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled from readily available building blocks with full control over the remote stereocenters, enabling the total synthesis to be completed in 16 steps (LLS).
Assuntos
Antimaláricos , Ésteres , Boro , Macrolídeos , EstereoisomerismoRESUMO
There is an increasing attention in developing highly efficient and reusable palladium-based catalysts used for the coupling reactions due to the high cost of palladium metal salts. Magnetically separable palladium nanoparticles have a high potential to be used as catalysts in numerous organic reactions due to their facile separation from the reaction medium by an external magnet. Herein, NiFe2O4 supported palladium nanoparticles (Pd/NiFe2O4) were successfully prepared by impregnation and reduction method in water and used as catalysts for Sonogashira cross-coupling reactions. Magnetically separable Pd/NiFe2O4 catalysts were found to be highly active and reusable in this reaction. Pd/NiFe2O4 provided an outstanding turnover frequency value (106.4 h-1) in the reaction between phenylacetylene and iodobenzene in ethanol at 70 °C and it was also found to be highly active in the water. Magnetically separable Pd/NiFe2O4 exhibited high catalytic performance even after the tenth use in this reaction.
Assuntos
Nanopartículas Metálicas , Paládio , Catálise , Compostos Férricos , Níquel , ÁguaRESUMO
The AgOTf-catalyzed reaction of C-2 substituted pyrrole hydrazones having an N-propargyl group was studied. The selective 6-endo-dig mode of cyclization was observed, giving rise to the formation of pyrrole-fused C,N-cyclic azomethine imine derivatives. The reaction of one azomethine imine derivative with various dipolarophiles resulted in the formation of cycloadducts having a pyrazolopyrrolopyrazine skeleton. The aromaticity of C,N-cyclic azomethine imines as well as that of pyrazolopyrrolopyrazines was determined by calculating of nucleus-independent chemical shifts values.
RESUMO
A concise and regioselective approach to the synthesis of chromenopyridine and chromenopyridinone derivatives was developed. The synthetic strategy relies on the O-propargylation of aromatic hydroxyaldehydes followed by reaction with propargylamine. The intramolecular cycloaddition reaction between the alkyne and azadiene, which is formed as an intermediate, furnished the desired skeletons.