Synthesis and Evaluation of Antimicrobial Activity and Molecular Dock - ing of New N-1,3-thiazol-2-ylacetamides of Condensed Pyrido[3',2':4,5] furo(thieno)[3,2-d]pyrimidines.
Curr Top Med Chem
; 20(24): 2192-2209, 2020.
Article
em En
| MEDLINE
| ID: mdl-32598259
ABSTRACT
BACKGROUND:
From the literature it is known that many derivatives of fused thienopyrimidines and furopyrimidines possess broad spectrum of biological activity.OBJECTIVES:
The current studies describe the synthesis and evaluation of antimicrobial activity of some new N-1,3-thiazol-2-ylacetamides of pyrido[3',2'4,5]furo(thieno)[3,2-d]pyrimidines.METHODS:
By cyclocondensation of ethyl 1-aminofuro(thieno)[2,3-b]pyridine-2-carboxylates 1with formamide were converted to the pyrido[3',2'4,5]furo(thieno)[3,2-d]pyrimidin-7(8)-ones 2.Alkylation of compound 2 with 2-chloro-N-1,3-thiazol-2-ylacetamide led to the aimed N-1,3-thiazol-2-ylaceta-mides of pyrido[3',2'4,5]furo(thieno)[3,2-d]pyrimidines 3. Starting from compound 2 the relevant S-alkylated derivatives of pyrido[3',2'4,5]furo(thieno)[3,2-d]pyrimidines 6 were also synthesized.RESULTS:
All the compounds showed antibacterial activity to non-resistant strains. Compounds 3a-3m showed antibacterial activity with MIC/MBC at 0.08-2.31 mg/mL/0.11-3.75 mg/mL .The two most active compounds, 3j and 6b, appeared to be more active towards MRSA than the reference drugs. Half of the tested compounds appeared to be equipotent/more potent than ketoconazole and more potent than bifonazole. The docking analysis provided useful information about the interactions occurring between the tested compounds and the different enzymes.CONCLUSION:
Gram-negative and Gram-positive bacteria and fungi showed different response towards tested compounds, indicating that different substituents may lead to different modes of action or that the metabolism of some bacteria/fungi was better able to overcome the effect of the compounds or adapt to it.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Triazóis
/
Antibacterianos
/
Antifúngicos
Limite:
Humans
Idioma:
En
Revista:
Curr Top Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Armênia