1174672-29-7Relevant academic research and scientific papers
Synthesis and 2D-QSAR studies of neolignan-based diaryl-tetrahydrofuran and -furan analogues with remarkable activity against Trypanosoma cruzi and assessment of the trypanothione reductase activity
Hartmann, Ana Paula,de Carvalho, Marcelo Rodrigues,Bernardes, Lilian Sibelle Campos,de Moraes, Milena Hoehr,de Melo, Eduardo Borges,Lopes, Carla Duque,Steindel, Mario,da Silva, Jo?o Santana,Carvalho, Ivone
, p. 187 - 199 (2017)
Two series of diaryl-tetrahydrofuran and -furan were synthesised and screened for anti-trypanosomal activity against trypomastigote and amastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. Based on evidence that modification of a natural product may result in a more effective drug than the natural product itself, and using known neolignan inhibitors veraguensin 1 and grandisin 2 as templates to synthesise simpler analogues, remarkable anti-trypanosomal activity and selectivity were found for 3,5-dimethoxylated diaryl-furan 5c and 2,4-dimethoxylated diaryl-tetrahydrofuran 4e analogues with EC50 0.01 μM and EC50 0.75 μM, respectively, the former being 260-fold more potent than veraguensin 1 and 150-fold better than benznidazole, the current available drugs for Chagas disease treatment. The ability of the most potent anti-trypanosomal compounds to penetrate LLC-MK2 cells infected with T. cruzi amastigotes parasite was tested, which revealed 4e and 5e analogues as the most effective, causing no damage to mammalian cells. In particular, the majority of the derivatives were non-toxic against mice spleen cells. 2D-QSAR studies show the rigid central core and the position of dimethoxy-aryl substituents dramatically affect the anti-trypanosomal activity. The mode of action of the most active anti-trypanosomal derivatives was investigated by exploring the anti-oxidant functions of Trypanothione reductase (TR). As a result, diarylfuran series displayed the strongest inhibition, highlighting compounds 5d-e (IC50 19.2 and 17.7 μM) and 5f-g (IC50 8.9 and 7.4 μM), respectively, with similar or 2-fold higher than the reference inhibitor clomipramine (IC50 15.2 μM).
Gold-Catalyzed stereocontrolled synthesis of 2,3-Bis(acetoxy)-1,3-dienes
Huang, Xiaogen,De Haro, Teresa,Nevado, Cristina
supporting information; experimental part, p. 5904 - 5908 (2010/03/03)
A 1,4-bis(propargyl acetates) undergo a highly selective tandem 1,2-/1,2-Bis(acetoxy) migration to give 2,3-Bis(acetoxy)-1,3-dienes, that, depending on the catalyst of choice,(1Z,3Z) or (1Z,3E and 1E,3Z)-1,3-dienes can be obtained in a stereocontrolled manner. It was found that the 1,2-Bis(acetoxy) migration was favored in all studied cases and no allene product was observed in the reaction mixtures. It was also found that more e sterically demanding substrate dramatically improved the selectivity thereby revealing the key role of sterics in the stereocontrol of these transformations. The results show that the choice of the acetoxy migrating first seemed to be of key importance and is determined both by the electronic character and sterical bulkiness of substituents at the propargylic position.
