Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism studies

2018 ◽  
Vol 26 (14) ◽  
pp. 3975-3981 ◽  
Author(s):  
Meng Lei ◽  
Huayun Feng ◽  
Enhe Bai ◽  
Hui Zhou ◽  
Jia Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Boronic Acid ◽  
Proteasome Inhibitors ◽  
Activity Relationship ◽  
In Vivo Evaluation ◽  
Design Synthesis ◽  
Structure Activity ◽  
Anti Cancer

3D-QSAR-aided design, synthesis, in vitro and in vivo evaluation of dipeptidyl boronic acid proteasome inhibitors and mechanism studies

2016 ◽  
Vol 24 (11) ◽  
pp. 2576-2588 ◽  
Author(s):  
Meng Lei ◽  
Huayun Feng ◽  
Cheng Wang ◽  
Hailing Li ◽  
Jingmiao Shi ◽  
...  
Keyword(s):  
Boronic Acid ◽  
Proteasome Inhibitors ◽  
3D Qsar ◽  
In Vivo Evaluation ◽  
Design Synthesis ◽  
Aided Design

Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid–based proteasome inhibitors

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5927-5937 ◽  
Author(s):  
Encouse B. Golden ◽  
Philip Y. Lam ◽  
Adel Kardosh ◽  
Kevin J. Gaffney ◽  
Enrique Cadenas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Tumor Cell ◽  
Green Tea ◽  
Boronic Acid ◽  
Proteasome Inhibitors ◽  
Green Tea Polyphenols ◽  
Tumor Cell Death

Abstract The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this “miracle herb” in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid–based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non–boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

Synthesis of new generation triazolyl- and isoxazolyl-containing 6-nitro-2,3-dihydroimidazooxazoles as anti-TB agents: in vitro, structure–activity relationship, pharmacokinetics and in vivo evaluation

2015 ◽  
Vol 13 (12) ◽  
pp. 3610-3624 ◽  
Author(s):  
Gurunadham Munagala ◽  
Kushalava Reddy Yempalla ◽  
Samsher Singh ◽  
Sumit Sharma ◽  
Nitin Pal Kalia ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
In Vivo Evaluation ◽  
Structure Activity ◽  
New Generation

Promising nitroimidazoloxazole scaffold gives another novel triazolyl-containing 6-nitro-2,3-dihydroimidazooxazole as anti-TB lead.

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