Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine Derivatives for HCV Inhibition

نویسندگان

  • Duozhi Chen
  • Jieyun Cai
  • Junjun Cheng
  • Chenxu Jing
  • Junlin Yin
  • Jiandong Jiang
  • Zonggen Peng
  • Xiaojiang Hao
چکیده

Lycorine is reported to be a multifunctional compound. We previously showed that lycorine is an HCV inhibitor with strong activity. Further research on the antivirus mechanism indicated that lycorine does not affect the enzymes that are indispensable to HCV replication but suppresses the expression of Hsc70 in the host cell to limit HCV replication. However, due to the cytotoxicity and apoptosis induction of lycorine, lycorine is unsafe to be a anti-HCV agent for clinical application. As a result of increasing interest, its structure was optimized for the first time and a novel series of lycorine derivatives was synthesized, all of which lost their cytotoxicity to different degrees. Structure-activity analysis of these compounds revealed that disubstitution on the free hydroxyl groups at C1 and C2 and/or degradation of the benzodioxole group would markedly reduce the cytotoxicity. Furthermore, an α, β-unsaturated ketone would improve the HCV inhibitory activity of lycorine. The C3-C4 double bond is crucial to the anti-HCV activity because hydrogenation of this double bond clearly weakened HCV inhibition.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase

UNLABELLED BACKGROUND Alzheimer's disease (AD) is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE) inhibitors and bivalent cholinesterase (ChE) inhibitors represent new treatments for AD. FINDINGS A series of lycorine derivatives (1-10) were synthesized and evaluated for anti-cholinesterase activity. Resul...

متن کامل

Design and Synthesis of New Benzimidazole and Pyrimidine Derivatives as α-glucosidase Inhibitor

In an endeavor to find a novel series of antihyperglycemic agents, new benzimidazole and pyrimidine derivatives were successfully synthesized efficiently in high yield with high purity, starting from amino acids in the presence of phosphorus oxychloride (POCl3). The synthesized compounds were identified by 1H-NMR, 13C-NMR, FT-IR spectroscopic techniques and elemental analysis. All products were...

متن کامل

Design and Synthesis of New Benzimidazole and Pyrimidine Derivatives as α-glucosidase Inhibitor

In an endeavor to find a novel series of antihyperglycemic agents, new benzimidazole and pyrimidine derivatives were successfully synthesized efficiently in high yield with high purity, starting from amino acids in the presence of phosphorus oxychloride (POCl3). The synthesized compounds were identified by 1H-NMR, 13C-NMR, FT-IR spectroscopic techniques and elemental analysis. All products were...

متن کامل

Novel N-2-(Furyl)-2-(chlorobenzyloxyimino) ethyl Piperazinyl Quinolones: Synthesis, Cytotoxic Evaluation and Structure-activity Relationship

Quinolone antibacterials are one of the most important classes of pharmacological agents known as potent inhibitors of bacterial DNA gyrase and topoisomerase IV that efficiently inhibit DNA replication and transcription by generating several double-stranded DNA break. Some quinolone derivatives demonstrated inhibitory potential against eukaryote topoismarase II and substantial dose-dependent cy...

متن کامل

Predictive Modeling of Phenylpiperazine Derivatives for Renin Inhibition.

The renin–angiotensin–aldosterone system is the well established endocrine system having significant role in preserving hemodynamic stability. Renin is secreted from the juxtaglomerular cells of the kidney. Phenylpiperazine derivatives have been reported as human renin inhibitor. To perform predictive QSAR modeling for 27 phenylpiperazine derivatives as renin enzyme inhibitors. The IC50 values ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2015