Journal article

Publication year: 2020

Pages: 14451-14460

Journal: ACS Omega

Volume number: 5

Issue number: 24

ISSN: 2470-1343

Open access status: Gold

DOI Link: https://doi.org/10.1021/acsomega.0c01065

Publisher: American Chemical Society

Abstract: 
Hirsutellide A is nature-derived cyclic hexadepsipeptide with reported antimycobacterial and antiplasmodial activities. To verify its structure, hirsutellide A was synthesized following a solution-phase peptide synthesis approach. A detailed analysis of the H-1 and C-13 NMR spectra of the synthesized compound revealed structural variation from what had been originally assigned for hirsutellide A, despite the use of identical building blocks. This variation occurred at the two allo-Ile moieties. To investigate the structure-activity relationship, the depsipeptide and peptide analogues of hirsutellide A were prepared and tested for antimycobacterial and antiplasmodial activities. The compounds displayed antiplasmodial potency against Plasmodium falciparum 3D7 while showing weak or no activity against Mycobacterium tuberculosis H37Rv. The drug-likeness of the series was assessed through in vitro absorption, distribution, metabolism, and excretion (ADME) profiling, revealing systematic differences between the pharmacokinetic properties of cyclic hexapeptides and hexadepsipeptides.

Harvard Citation style: Sahile, H., Martinez-Martinez, M., Dillenberger, M., Becker, K. and Imming, P. (2020) Synthesis and Evaluation of Antimycobacterial and Antiplasmodial Activities of Hirsutellide A and Its Analogues, ACS Omega, 5(24), pp. 14451-14460. https://doi.org/10.1021/acsomega.0c01065

APA Citation style: Sahile, H., Martinez-Martinez, M., Dillenberger, M., Becker, K., & Imming, P. (2020). Synthesis and Evaluation of Antimycobacterial and Antiplasmodial Activities of Hirsutellide A and Its Analogues. ACS Omega. 5(24), 14451-14460. https://doi.org/10.1021/acsomega.0c01065