Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents,Journal of Medicinal Chemistry

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Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-30 , DOI: 10.1021/acs.jmedchem.4c00666
Saroj Maji _{1,

2} , Sariyah Akhtar ₃ , Sabyasachi Halder _{1,

2} , Indranil Chatterjee ₁ , Devesh Pratap Verma ₃ , Neeraj Kumar Verma _{3,

4} , Jyotshana Saroj ₃ , Deepanshi Saxena ₅ , Rahul Maitra ₅ , Juhi Sharma ₆ , Bhawana Sharma ₁ , Hidehiro Sakurai ₇ , Kalyan Mitra _{2,

6} , Sidharth Chopra _{2,

5} , Jimut Kanti Ghosh _{2,

3} , Gautam Panda _{1,

2}

Affiliation

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism. Importantly, several of the synthesized peptides were found to be appreciably nonhemolytic against hRBCs and noncytotoxic against mammalian 3T3 cells. In vivo efficacy studies of the potent and least cytotoxic peptide 6a demonstrated clearance of bacteria from the spleen, liver, lung, and blood of mice infected with S. aureus ATCC 25923.

中文翻译：

Corannulene 氨基酸衍生的水溶性两亲性巴基碗作为广谱膜靶向抗菌剂

迄今为止，球环烯的使用在材料科学领域受到限制，但由于其在水性环境中的不溶解性和合成的不可行性，其在生物医学研究中的应用尚未建立。在此，我们详细介绍了一个新的高度弯曲的 π 共轭的含有非天然 α-氨基酸 (CAA) 衍生物家族的开发，以克服这一挑战。这些 CAA 已被扩展为合成含有 Corannulene 的水溶性阳离子肽 (CCP) 的新成分，该肽通过膜损伤机制对广谱病原菌和耐药细菌表现出抑制活性。重要的是，发现几种合成的肽对 hRBC 明显无溶血作用，对哺乳动物 3T3 细胞无细胞毒性。对有效且细胞毒性最小的肽6a的体内功效研究表明，可以清除感染金黄色葡萄球菌的小鼠的脾、肝、肺和血液中的细菌。金黄色葡萄球菌ATCC 25923。

更新日期：2024-08-30

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