Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents
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. <i>In vivo</i> efficacy studies of the potent and least cytotoxic peptide <b>6a</b> demonstrated clearance of bacteria from the spleen, liver, lung, and blood of mice infected with <i>S</i>. <i>aureus</i> ATCC 25923.
Authors
- Devesh Pratap Verma
- Sariyah Akhtar
- Jyotshana Saroj
- Jimut Kanti Ghosh (ORCID: https://orcid.org/0000-0001-7957-6296)
- Sabyasachi Halder
- Deepanshi Saxena (ORCID: https://orcid.org/0000-0001-9785-6224)
- Saroj Maji
- Hidehiro Sakurai (ORCID: https://orcid.org/0000-0001-5783-4151)
- Gautam Panda (ORCID: https://orcid.org/0000-0003-4248-4579)
- Sidharth Chopra (ORCID: https://orcid.org/0000-0001-8823-6074)
- Bhawana Sharma (ORCID: https://orcid.org/0000-0002-0239-2154)
- Kalyan Mitra (ORCID: https://orcid.org/0000-0002-7252-1716)
- Neeraj Kumar Verma (ORCID: https://orcid.org/0000-0002-9688-7042)
- Juhi Sharma (ORCID: https://orcid.org/0000-0002-9820-3820)
- I. Chatterjee (ORCID: https://orcid.org/0000-0001-8685-7328)
- Rahul Maitra (ORCID: https://orcid.org/0000-0002-2674-0694)
Institutions
- Central Drug Research Institute (IN)
- The University of Osaka (JP)
- Academy of Scientific and Innovative Research (IN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c00666
- Citations
- 5
- Primary Topic
- Fullerene Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.25
Funders
- Department of Science and Technology, Ministry of Science and Technology, India
- Council of Scientific and Industrial Research, India