182217-53-4Relevant articles and documents
Palladium (II)-catalysed intramolecular C–H functionalizations: Efficient synthesis of kealiinine C and analogues
Saha, Debasmita,Stolarzewicz, Izabela,Bahadur, Vijay,Sharma, Upendra K.,Voskressensky, Leonid G.,Sharma, Anuj,Singh, Brajendra K.,Van der Eycken, Erik V.
, p. 233 - 238 (2018/07/03)
An efficient palladium-catalysed C–H functionalization sequence has been developed for the synthesis of 2-aminoimidazole alkaloids (Kealiinine C) and its analogues. This protocol proceeds via iodocyclisation of propargylguanidines followed by intramolecul
Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90
Jiang, Long,Yin, Ruijuan,Wang, Xueting,Dai, Jiajia,Li, Jing,Jiang, Tao,Yu, Rilei
supporting information, p. 24 - 33 (2017/04/21)
In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.
From (+)-epigallocatechin gallate to a simplified synthetic analogue as a cytoadherence inhibitor for P. falciparum
Gemma, Sandra,Brogi, Simone,Patil, Pradeep R.,Giovani, Simone,Lamponi, Stefania,Cappelli, Andrea,Novellino, Ettore,Brown, Alan,Higgins, Matthew K.,Mustafa, Khairul,Szestak, Tadge,Craig, Alister G.,Campiani, Giuseppe,Butini, Stefania,Brindisi, Margherita
, p. 4769 - 4781 (2014/01/17)
Parasite derived surface antigen PfEMP1 is a virulence factor of the human malaria parasite. PfEMP1 variants have been implicated in the cytoadherence of P. falciparum infected erythrocytes (iRBC) to several binding receptors on host vascular endothelium. Among them, binding to ICAM-1 seems to be related to severe manifestations of the disease such as cerebral malaria. The binding site for iRBC has been mapped to the BED-side of the N-terminal immunoglobulin-like domain of ICAM-1, and the DE-loop appears to be critical for binding. To date (+)-EGCG is the unique small molecule anti-cytoadherence inhibitor probably mimicking the DE-loop of ICAM-1. Here we report the discovery of a tetrahydroisoquinoline derivative, a prototype of a novel class of cytoadherence inhibitors, and an analogue of the natural compound characterized by a synthetically accessible scaffold. Molecular modeling analysis of (+)-EGCG and its synthetic tetrahydroisoquinoline analogue rationalized their binding mode to PfEMP1, confirming their ability to mimic the DE-loop.
