Synthetic Strategies Towards the Generation of Penicillin-Containing Hybrids in the Search for Anticancer Activity.

An extended library of hybrids that combined a penicillin derivative with a peptoid moiety was designed and synthetized using either a solid-phase or a mixed solid-phase/solution-phase strategy. The library was further evaluated for antiproliferative activity. While none of the different synthesized compounds showed significant cytotoxicity against a normal cell line, tumor cell results drew several conclusions, when comparing with our reference, the highly active triazolylpeptidyl penicillin derivative, TAF7f.

Synergistic antitumor effect of a penicillin derivative combined with thapsigargin in melanoma cells.

Purpose: To investigate the effect of TAP7f, a penicillin derivative previously characterized as a potent antitumor agent that promotes ER stress and apoptosis, in combination with thapsigargin, an ER stress inducer, on melanoma cells.

Methods: The synergistic antiproliferative effect of TAP7f in combination with thapsigargin was studied in vitro in murine B16-F0 melanoma cells, and in human A375 and SB2 melanoma cells. In vivo assays were performed with C57BL/6J mice challenged with B16-F0 cells.

Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids.

The development of hybrid compounds led to the discovery of new pharmacologically active agents for some of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazole-containing structures designed by a molecular hybridization approach. Penicillin derivatives and amino acids were linked to amino acid and aromatic moieties through the formation of a 1,2,4-oxadiazole ring.

Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells.

We have previously examined the in vitro and in vivo antitumor action of TAP7f, a synthetic triazolylpeptidyl penicillin, on murine melanoma cells. In this work, we explored the signal transduction pathways modulated by TAP7f in murine B16-F0 and human A375 melanoma cells, and the contribution of some intracellular signals to the apoptotic cell death. TAP7f decreased ERK1/2 phosphorylation and increased phospho-p38, phospho-JNK and phospho-Akt levels.

Design, synthesis and cytotoxic evaluation of peptoid analogs of an anticancer active triazolylpeptidyl penicillin.

Encouraged by the antitumor activity exhibited by triazolylpeptidyl penicillins, we decided to synthesize and evaluate a library of peptoid analogs. The replacement of the dipeptide unit of the reference compound, TAP7f, was investigated. In addition, the effect of the triazole linking group on the biological activity of these new derivatives was evaluated, exchanging it with a glycine spacer.

A novel penicillin derivative induces antitumor effect in melanoma cells.

In this study, we explored the in-vitro and in-vivo mechanism of antitumor action of a novel synthetic nonantibiotic triazolylpeptidyl penicillin derivative, named TAP7f, on B16-F0 murine melanoma cells. In-vitro assays showed that TAP7f caused an inhibition of S phase progression and a concomitant decrease of the percentage of cells in G0/G1 phase. We also found that TAP7f treatment induced an apoptotic response characterized by an increase of the sub-G1 fraction of B16-F0 hypodiploid cells, the occurrence of cells with picnotic nuclei, and the detection of phosphatidylserine exposure on the outer side of the plasma membrane.