Expanding the structure-activity relationship of cytotoxic diphenyl macrocycles.

Autor: Chávez-Riveros A; Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico; Universidad Tecnológica de México-UNITEC MÉXICO - Campus Marina-Cuitláhuac, Norte 67 No. 2346, San Salvador Xochimanca, Azcapotzalco, DF 02870, Mexico. Electronic address: alejandra_chavez@my.unitec.edu.mx., Ramírez-Trinidad Á; Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico., Hernández-Vázquez E; Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico., Miranda LD; Department of Organic Chemistry, Chemistry Institute, UNAM, Circuito exterior S.N., Ciudad Universitaria, Coyoacán, México DF 04510, Mexico. Electronic address: lmiranda@unam.mx.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2022 Apr 15; Vol. 62, pp. 128628. Date of Electronic Publication: 2022 Feb 16.
DOI: 10.1016/j.bmcl.2022.128628
Abstrakt: 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.
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Databáze: MEDLINE
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