Expanding the structure-activity relationship of cytotoxic diphenyl macrocycles.

Bioorg Med Chem Lett

Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico. Electronic address:

Published: April 2022

Twenty-four biaryl tetrapeptide macrocycles were synthesized as an extension of our previous work. Two groups of compounds were constructed for establishing a structure-activity relationship: one having an aromatic substituent at α-position of one exo-peptide and the other group with a variation in the size of the lipophilic chain. Compound 13t had the best cytotoxicity from all the compounds tested (in a panel of six human cancer cell lines) and low toxicity on one healthy cell line. The study identified the lipophilic chain as the main structural moiety for improving the biological activity, being the seven-carbon chain the optimal length. On the other hand, the aromatic rings at α-position did not enhance the cytotoxicity.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2022.128628DOI Listing

Publication Analysis

Top Keywords

structure-activity relationship
8
lipophilic chain
8
expanding structure-activity
4
relationship cytotoxic
4
cytotoxic diphenyl
4
diphenyl macrocycles
4
macrocycles twenty-four
4
twenty-four biaryl
4
biaryl tetrapeptide
4
tetrapeptide macrocycles
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!