- Structural insight into the optimization of ethyl 5-hydroxybenzo[g]indol-3-carboxylates and their bioisosteric analogues as 5-LO/m-PGES-1 dual inhibitors able to suppress inflammation
-
The release of pro-inflammatory mediators, such as prostaglandines (PGs) and leukotrienes (LTs), arising from the arachidonic acid (AA) cascade, play a crucial role in initiating, maintaining, and regulating inflammatory processes. New dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase-1 (mPGES-1), that block, at the same time, the formation of PGE2 and LTs, are currently emerged as a highly interesting drug candidates for better pharmacotherapie of inflammation-related disorders. Following our previous studies, we here performed a detailed structure-based design of benzo[g]indol-3-carboxylate derivatives, disclosing several new key factors that affect both enzyme activity. Ethyl 2-(3,4-dichlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (4b, RAF-01) and ethyl 2-(3,4-dichlorophenyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (7h, RAF-02) emerged as the most active compounds of the series. Additionally, together with selected structure based analogues, both derivatives displayed significant in vivo anti-inflammatory properties. In conclusion, modeling and experimental studies lead to the discovery of new candidate compounds prone to further developments as multi-target inhibitors of the inflammatory pathway.
- Bruno, Ferdinando,Errico, Suann,Pace, Simona,Nawrozkij, Maxim B.,Mkrtchyan, Arthur S.,Guida, Francesca,Maisto, Rosa,Olga?, Abdurrahman,D'Amico, Michele,Maione, Sabatino,De Rosa, Mario,Banoglu, Erden,Werz, Oliver,Fiorentino, Antonio,Filosa, Rosanna
-
p. 946 - 960
(2018/07/24)
-
- Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains
-
Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI)
- Mai, Antonello,Artico, Marino,Rotili, Dante,Tarantino, Domenico,Clotet-Codina, Imma,Armand-Ugón, Mercedes,Ragno, Rino,Simeoni, Silvia,Sbardella, Gianluca,Nawrozkij, Maxim B.,Samuele, Alberta,Maga, Giovanni,Esté, José A.
-
p. 5412 - 5424
(2008/03/13)
-
- Substituted 6-benzyl-4-oxopyrimidines, process for their preparation and pharmaceutical compositions containing them
-
The invention concerns novel substituted 6-benzyl-4-oxopyrimidines and pharmaceutically acceptable salts thereof. These compounds inhibit reverse transcriptase encoded by human immunodeficiency virus (HIV), and are useful to prevent and treat HIV infectio
- -
-
Page/Page column 7
(2008/06/13)
-
- Does the 2-methylthiomethyl substituent really confer high anti-HIV-1 activity to S-DABOs?
-
S-DABO derivatives containing the methylthiomethyl (MTM) group have been synthesized and tested for anti-HIV-1 activity in cell-based assay (MTT and p24 assays) and for their capability to target the HIV-1 reverse transcriptase in enzyme assays. Data of experiments lead to the conclusion that the introduction of a 2-MTM-thio side chain is not sufficient per se to significantly increase S-DABO's potency. Nevertheless, potent MTM-S-DABOs can be obtained by introducing a 2,6-difluorophenylmethyl moiety as a C-6 substituent.
- Sbardella, Gianluca,Mai, Antonello,Artico, Marino,Massa, Silvio,Marceddu, Tiziana,Vargiu, Laura,Marongiu, Maria Elena,La Colla, Paolo
-
-
- 5-alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin- 4(3H)-ones: Novel potent and selective dihydro-alkoxy-benzyl-oxopyrimidine derivatives
-
Molecular modeling analysis of compounds belonging to the recently published series of dihydro-alkoxy-benzyl-oxopyrimidines (DABOs), such as S- DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl- DABO derivatives as highly potent
- Mai, Antonello,Artico, Marino,Sbardella, Gianluca,Massa, Silvio,Novellino, Ettore,Greco, Giovanni,Loi, Anna Giulia,Tramontano, Enzo,Marongiu, Maria Elena,La Colla, Paolo
-
p. 619 - 627
(2007/10/03)
-