Browsing by Author "Gomes, P"
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- Amino acids as selective sulfonamide acylating agentsPublication . Gomes, P; Gomes, JRB; Rodrigues, M; Moreira, RAcylation of antimalarial and bacteriostatic sulfonamides with N-protected amino acids and peptides was carried out using standard peptide coupling methods. These acylation reactions are regioselective for the N-4 nitrogen atom of diazine-containing sulfonamides. In contrast, only N-1 coupling was found for sulfisoxazole, an isoxazole-based sulfonamide. Computational studies suggest that a combination of geometrical, thermodynamic and electronic factors are responsible for the different reactivities reported. (C) 2003 Elsevier Ltd. All rights reserved.
- Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamolPublication . Santos, C; Mateus, ML; dos Santos, AP; Moreira, R; de Oliveira, E; Gomes, PDipeptide esters of paracetamol were prepared in high yields. These compounds are quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines at pH 7.4 and 37 ° C. The reactivity is increased in sarcosine and proline peptides and decreased by bulky side chains at both the N- and C-terminal residues of the dipeptide carrier. Moreover, dipeptide esters of paracetamol did not affect the levels of hepatic glutathione. Thus, dipeptides seem promising candidates as carriers for cyclization-activated prodrugs. © 2005 Elsevier Ltd. All rights reserved.
- Different substitutions under drug pressure at protease codon 82 in HIV-1 subtype G compared to subtype B infected individuals including a novel 182M resistance mutationPublication . Camacho, R; Godinho, AR; Gomes, P; Abecasis, A; Vandamme, AM; Palma, C; Carvalho, AP; Cabanas, J; Goncalves, J
- Imidazolidin-4-one derivatives of primaquine as novel transmission-blocking antimalarialsPublication . Araujo, MJ; Bom, J; Capela, R; Casimiro, C; Chambel, P; Gomes, P; Iley, J; Lopes, F; Morais, J; Moreira, R; de Oliveira, E; do Rosario, V; Vale, NImidazolidin-4-one derivatives of primaquine were synthesized as potential double prodrugs of the parent drug. The title compounds inhibit the development of the sporogonic cycle of Plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. The imidazolidin-4-ones are very stable, both in human plasma and in pH 7.4 buffer, indicating that they are active per se. Thus, imidazolidin-4-ones derived from 8-aminoquinolines represent a new entry in antimalarial structure-activity relationships.
- Improved synthesis of amino acid and dipeptide chloromethyl esters using bromochloromethanePublication . Gomes, P; Santos, MI; Trigo, MJ; Castanheiro, R; Moreira, RPeptide chloromethyl esters are important compounds in prodrug synthesis. A simple, mild and efficient method for the synthesis of chloromethyl esters of N-blocked amino acids and dipeptides using exclusively bromochloromethane is reported. These N-blocked amino acid and dipeptide chloromethyl esters react readily with the carboxylic acid group of aspirin and with the sulfonamido group of the antimalarial sulfamethazine, to give the corresponding prodrugs.
- Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of primaquinePublication . Gomes, P; Araujo, MJ; Rodrigues, M; Vale, N; Azevedo, Z; Iley, J; Chambel, P; Morais, J; Moreira, RThe synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (+/-)-primaquine with N-alpha-protected amino acids, (ii) removal of the N-alpha-protecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic acid in the third step afforded 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. All products were isolated in good to excellent yields. Whereas imidazolidin-4-ones were formed as mixtures of all possible diastereomers in equal amounts, 1H-imidazo[2,1a]isoindole-2,5(3H,9bH)-diones were produced in a stereoselective fashion. The compounds hydrolyse very Slowly (t(1/2) 5-30 d) in pH 7.4 buffer to release primaquine. These primaquine derivatives are being submitted to biological assays, and preliminary results of their antimalarial activity are quite encouraging. (C) 2004 Elsevier Ltd. All rights reserved.
- Use of a new dual-antigen enzyme-linked Immunosorbent assay to detect and characterize the human antibody response to the human immunodeficiency virus type 2 envelope gp125 and gp36 glycoproteinsPublication . Marcelino, JM; Barroso, H; Goncalves, F; Silva, SM; Novo, C; Gomes, P; Camacho, R; Taveira, NA dual-antigen enzyme-linked immunosorbent assay specific for human immunodeficiency virus type 2 (HIV-2) envelope proteins, ELISA-HIV2, was developed with two new recombinant polypeptides, rpC2-C3 and rgp36, derived from the HIV-2 envelope. The diagnosti