959658-87-8Relevant academic research and scientific papers
Imidazo[2,1-a]isoindole scaffold as an uncharted structure active on Leishmania donovani
Arsène, Sobinson,Gómez-Pérez, Verónica,Escarcena, Ricardo,Abengózar, María ángeles,García-Hernández, Raquel,Nácher-Vázquez, Montserrat,San Feliciano, Arturo,Gamarro, Francisco,Rivas, Luis,Olmo, Esther del
, (2019/08/16)
The human protozoan parasites Leishmania donovani and L. infantum are the causative agents of visceral leishmaniasis, as such, responsible for approximately 30,000 deaths annually. The available chemotherapeutic treatments are reduced to a few drugs whose effectiveness is limited by rising drug resistance/therapeutic failure, and noxious side-effects. Therefore, new therapeutic hits are needed. Compounds displaying the imidazo[2,1-a]isoindole skeleton have shown antichagasic, anti-HIV, antimalarial and anorectic activities. Here, we report the leishmanicidal activity of thirty one imidazo[2,1-a]isoindol-5-ol derivatives on promastigotes and intracellular amastigotes of L. donovani. Eight out of thirty one assayed compounds showed EC50 values ranging between 1 and 2 μM with selectivity indexes from 29 to 69 on infected THP-1 cells. Six compounds were selected for further elucidation of their leishmanicidal mechanism. In this regard, compound 29, the imidazoisoindolol with the highest activity on intracellular amastigotes, induced an early decrease of intracellular ATP levels, as well as mitochondrial depolarization, together with a partial plasma membrane destructuration, as assessed by transmission electron microscopy. Consequently, the inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound, even when other additional targets cannot be ruled out. In all, the results supported the inclusion of the imidazoisoindole scaffold for the development of new leishmanicidal drugs.
NHC-catalyzed oxidative cyclization reactions of 2-alkynylbenzaldehydes under aerobic conditions: Synthesis of O-Heterocycles
Park, Jong Hyub,Bhilare, Sachin V.,Youn, So Won
, p. 2228 - 2231 (2011/07/09)
Chemical equations presented. An NHC-catalyzed, regio- and stereoselective oxidative cyclization of o-alkynylbenzaldehydes bearing an unactivated alkyne moiety as an internal electrophile has been developed to afford phthalides and isocoumarins. A single organocatalytic system enabled two sequential C-O bond formations to take place in an atom economical manner via highly efficient dual activation. Molecular oxygen in air could be utilized as a source of an oxygen atom for the oxidation of aldehydes to the corresponding benzoic acids under our newly developed reagent system.
Anti-HIV activity of stilbene-related heterocyclic compounds
Bedoya, Luis M.,del Olmo, Esther,Sancho, Rocio,Barboza, Bianca,Beltran, Manuela,Garcia-Cadenas, Ana E.,Sanchez-Palomino, Sonsoles,Lopez-Perez, Jose L.,Munoz, Eduardo,Feliciano, Arturo San,Alcami, Jose
, p. 4075 - 4079 (2007/10/03)
Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-κB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-κB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-κB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.
