Asymmetric Synthesis and Evaluation of Danshensu-Cysteine Conjugates as Novel Potential Anti-Apoptotic Drug Candidates

International Journal of Molecular Sciences

Li-Long Pan¹  Jie Wang²  Yao-Ling Jia²  Hong-Ming Zheng¹  Yang Wang²  Yi-Zhun Zhu¹ 

[1] Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China; E-Mails:;Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China; E-Mails:

关键词: Danshensu derivative;    apoptosis;    asymmetric synthesis;    endothelial cells;   

DOI  :  10.3390/ijms16010628

来源: mdpi

【 摘 要 】

We have previously reported that the danshensu-cysteine conjugate N-((R)-3-benzylthio-1-methoxy-1-oxo-2-propanyl)-2-acetoxy-3-(3,4-diacetoxyphenyl) propanamide (DSC) is a potent anti-oxidative and anti-apoptotic agent. Herein, we further design and asymmetrically synthesize two diastereoisomers of DSC and explore their potential bioactivities. Our results show that DSC and its two diastereoisomers exert similar protective effects in hydrogen peroxide (H₂O₂)-induced cellular injury in SH-SY5Y cells, as evidenced by the increase of cell viability, superoxide dismutase (SOD), and reduced glutathione (GSH) activity, and glutathione peroxidase (GPx) expression, and the decrease of cellular morphological changes and nuclear condensation, lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) production. In H₂O₂-stimulated human umbilical vein endothelial cells (HUVEC), DSC concentration-dependently attenuates H₂O₂-induced cell death, LDH release, mitochondrial membrane potential collapse, and modulates the expression of apoptosis-related proteins (Bcl-2, Bax, caspase-3, and caspase-9). Our results provide strong evidence that DSC and its two diastereoisomers have similar anti-oxidative activity and that DSC exerts significant vascular-protective effects, at least in part, through inhibition of apoptosis and modulation of endogenous antioxidant enzymes.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.