Design, synthesis and structure-activity relationship of novel Relacin analogs as inhibitors of Rel proteins

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• 作者：Ezequiel Wexselblatt ; Ilana Kaspy ; Gad Glaser ; Joshua Katzhendler ; Eylon Yavin
• 关键词：Antibacterial ; Stringent Response ; (p)ppGpp ; RelA ; Purine
• 刊名：European Journal of Medicinal Chemistry
• 出版年：December, 2013
• 年：2013
• 卷：70
• 期：Complete
• 页码：497-504
• 全文大小：579 K

文摘

Rel proteins in bacteria synthesize the signal molecules (p)ppGpp that trigger the Stringent Response, responsible for bacterial survival. Inhibiting the activity of such enzymes prevents the Stringent Response, resulting in the inactivation of long-term bacterial survival strategies, leading to bacterial cell death. Herein, we describe a series of deoxyguanosine-based analogs of the Relacin molecule that inhibit in聽vitro the synthetic activity of Rel proteins from Gram positive and Gram negative bacteria, providing a deeper insight on the SAR for a better understanding of their potential interactions and inhibitory activity. Among the inhibitors evaluated, compound 2d was found to be more effective and potent than our previously reported Relacin.