31165-12-5Relevant academic research and scientific papers
The synthetic and biological studies of discorhabdins and related compounds
Wada, Yasufumi,Harayama, Yu,Kamimura, Daigo,Yoshida, Masako,Shibata, Tomoyuki,Fujiwara, Kousaku,Morimoto, Koji,Fujioka, Hiromichi,Kita, Yasuyuki
, p. 4959 - 4976 (2011/08/06)
Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(iii) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the β-amino alcohols with the hypervalent iodine reagent C6F 5I(OCOCF3)2, the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN3 and the bridged ether synthesis with HBr-AcOH as the key reactions. All the synthesized compounds were evaluated by in vitro MTT assay for cytotoxic activity against the human colon cancer cell line HCT-116. Furthermore, the discorhabdin A oxa analogues were also evaluated against four kinds of tumor model cells, a human colon cancer cell line (WiDr), a human prostate cancer cell line (DU-145) and murine leukemia cell lines (P388 and L1210). For the identification of the target, discorhabdin A and the discorhabdin A oxa analogue were evaluated by an HCC panel assay. In the test, discorhabdins could have a novel mode of action with the tumor cells. The Royal Society of Chemistry 2011.
HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation
De Luca, Laura,De Grazia, Sara,Ferro, Stefania,Gitto, Rosaria,Christ, Frauke,Debyser, Zeger,Chimirri, Alba
, p. 756 - 764 (2011/03/20)
This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)- 5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative 8e to assume the same binding mode of MK-0518 and GS 9137.
