Pentacloreto de nióbio (NbCl5) : um novo catalisador ácido de Lewis aplicado na síntese de 3,4-dihidropirimidinonas

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In vitro Anti-HMPV activity of new synthetic phenytoin derivatives

New derivatives of synthetic 5,5-diphenylhydantoin (phenytoin) were prepared by N-alkylation with 1,3-dibromopropane. Subsequent treatment with sodium azide led to the respective azide. Reaction of the azide with phenylacetylene and 2-hydroxy-3-butyne and oxidation of the resulting alcohol with MnO2 resulted in three triazolic compounds that were evaluated in vitro for their antiviral activity against human metapneumovirus (HMPV). 5,5-Diphenyl-3-[3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl]imidazolidine-2,4-dione was the most active of the three compounds tested, with selectivity index of 129.87, even higher than ribavirin, the control substance. The three compounds showed activity in the early stages of viral replication presenting virucidal activity and binding to cellular receptors, preventing the adsorption of viral particles. These compounds showed higher activity in both experiments, inhibiting 98.3% of infection as virucidal and 98.9% when interacting with cellular receptors. Furthermore, they showed 73.8% of activity during the penetration of HMPV particles into cells. The derivative 3-{3-[4-(1-hydroxyethyl)-1H-1,2,3-triazol-1-yl]propyl}-5,5-diphenylimidazolidine-2,4-dione presented a mild anti-HMPV activity, with selectivity index of 2.74. 3-[3-(4-acetyl-1H-1,2,3-triazol-1-yl)propyl]-5,5-diphenylimidazolidine-2,4-dione inhibited less than 50% of HMPV replication

Synthesis, characterization and in vitro anticancer activity of Novel 8,4’ : oxyneolignan analogues

Neolignans are a class of natural products with a wide range of biological effects. These substances are of great synthetic and biological interest, especially in searching for novel anticancer agents. In this paper, we report the synthesis of a new subclass of 8,4’-oxyneolignan analogues (β-ketoethers and β-ketoesters) and their cell viability assay on twenty four different cancer cells, among leukemias and carcinomas. Three compounds inhibited the growth of most human cancer cells. 2-Oxo-2-phenylethyl(2E)-3-[4-(2-oxo-2-phenylethoxy) phenyl]prop-2-enoate showed an antiproliferative activity superior to doxorubicin for U-87, U-138 MG and H1299 cell types and (E)-2-oxo-2-phenylethyl 3-(3-methoxy-4-(2-oxo-2-phenylethoxy)phenyl)acrylate was found to be very selective, demonstrating a growth inhibition of 92.0% against KG-1 cells. Furthermore, 1-oxo-1-phenylpropan-2-yl cinnamate exhibited significant inhibition activity in a range of 52.2 to 91.2% against twelve kinds of leukemia cell lines, revealing excellent results and very comparable to the reference drug

Studies on the niobium pentachloride-mediated nucleophilic additions to an enantiopure cyclic N-acyliminium ion derived from (S)-malic acid

A adição nucleofílica de vários nucleófilos (alilsilano, silil enol éter da acetofenona, indol e Nsulfonilindol) ao íon N-acilimínio enantiopuro 1a, derivado do ácido (S)-málico, promovida por pentacloreto de nióbio é descrita. Os produtos foram obtidos em bons rendimentos e em diastereosseletividades variáveis dependendo do volume estérico do nucleófilo. Os melhores resultados foram obtidos com a adição de indóis.The nucleophilic addition of several nucleophiles (allyltrimethylsilane, silyl enol ether from acetophenone, indole and N-sulfonylindole) to the enantiopure cyclic N-acyliminium ion 1a, derived from (S)-malic acid, promoted by niobium pentachloride is described. The products were obtained in good yields and in variable diastereoselectivities depending on the steric bulkiness of the nucleophile. The best results were obtained with the addition of indoles

Pentacloreto de nióbio (NbCl5) : um novo catalisador ácido de Lewis aplicado na síntese de 3,4-dihidropirimidinonas

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Studies on the niobium pentachloride-mediated nucleophilic additions to an enantiopure cyclic N-acyliminium ion derived from (S)-malic acid

A adição nucleofílica de vários nucleófilos (alilsilano, silil enol éter da acetofenona, indol e Nsulfonilindol) ao íon N-acilimínio enantiopuro 1a, derivado do ácido (S)-málico, promovida por pentacloreto de nióbio é descrita. Os produtos foram obtidos em bons rendimentos e em diastereosseletividades variáveis dependendo do volume estérico do nucleófilo. Os melhores resultados foram obtidos com a adição de indóis.The nucleophilic addition of several nucleophiles (allyltrimethylsilane, silyl enol ether from acetophenone, indole and N-sulfonylindole) to the enantiopure cyclic N-acyliminium ion 1a, derived from (S)-malic acid, promoted by niobium pentachloride is described. The products were obtained in good yields and in variable diastereoselectivities depending on the steric bulkiness of the nucleophile. The best results were obtained with the addition of indoles

Larvicidal activity of thiazolidinedione derivatives against Aedes aegypti larvae and toxicological studies with zebrafish embryos

BACKGROUND: Diseases caused by arboviruses are currently a worldwide public health problem. These diseases have the Aedes aegypti mosquito as the main transmission vector, and the main strategy to combat their spread is the interruption of the mosquito life cycle in its early stages. In this study, we synthesized thirteen thiazolidinedione derivatives (3a-3m) that were applied in a larvicide-based strategy against the Ae. aegypti vector and submitted to evaluation of toxicological effects. RESULTS: Microwave process intensification was utilized for the synthesis of thiazolidinedione derivatives (3a-3m). One thiazolidinedione derivative stands out (3a) with lethal concentrations (LC50-24 h) of 7.71 μg mL-1 (32.16 μmol L-1). It showed embryotoxicity to zebrafish at concentrations up to 1.0 μg mL-1 and mortality from 3.1 up to 100 μg mL-1. No biochemical disturbances occurred based on GST and LDH measurements. A para-substituted chlorine atom instead of hydrogen improves toxicity profile. CONCLUSION: The substitution pattern with a chlorine atom suggests a larvicidal activity. From the compounds tested, (Z)-5-(4-chlorobenzylidene)thiazolidine-2,4-dione (3a) was the most effective against Ae. Aegypti, showing embryotoxicity to zebrafish