Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues
摘要:
As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophagelike RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E-2 (PGE(2)). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for h5PLA(2), surface plasmon resonance (SPR) experiments were performed. (C) 2010 Elsevier Masson SAS. All rights reserved.
a transition metal, is described using a novel partner in the Suzuki–Miyaura couplingreaction catalyzed by Pd(OAc)2 and Ruphos as ligands. The products showed good to outstanding yields and broad functional group compatibility under optimal conditions. The sequentialsynthesis of non-symmetric terphenyls and the gram grade process highlight the approach's synthetic utility. DFT calculations have shown
As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophagelike RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E-2 (PGE(2)). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for h5PLA(2), surface plasmon resonance (SPR) experiments were performed. (C) 2010 Elsevier Masson SAS. All rights reserved.