Model Amphipathic Peptide Coupled with Tacrine to Improve Its Antiproliferative Activity

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Silva, S (Author) Other; Alves, C (Author) Other; Duarte, D (Author) Other; Costa, A (Author) Other; Sarmento, B (Author) Other; Almeida, AJ (Author) Other; Paula Gomes (Author) FCUP; Nuno Vale (Author) FMUP

Journal

Title: International Journal Of Molecular Sciences

Vol. 22

Pages: 1-17

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 6 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00T-83T

DOI: 10.3390/ijms22010242

Abstract (EN): Drug repurposing and drug combination are two strategies that have been widely used to overcome the traditional development of new anticancer drugs. Several FDA-approved drugs for other indications have been tested and have demonstrated beneficial anticancer effects. In this connection, our research group recently reported that Tacrine, used to treat Alzheimer's Disease, inhibits the growth of breast cancer MCF-7 cells both alone and in combination with a reference drug. In this view, we have now coupled Tacrine with the model amphipathic cell-penetrating peptide (CPP) MAP, to ascertain whether coupling of the CPP might enhance the drug's antiproliferative properties. To this end, we synthesized MAP through solid-phase peptide synthesis, coupled it with Tacrine, and made a comparative evaluation of the parent drug, peptide, and the conjugate regarding their permeability across the blood-brain barrier (BBB), ability to inhibit acetylcholinesterase (AChE) in vitro, and antiproliferative activity on cancer cells. Both MAP and its Tacrine conjugate were highly toxic to MCF-7 and SH-SY5Y cells. In turn, BBB-permeability studies were inconclusive, and conjugation to the CPP led to a considerable loss of Tacrine function as an AChE inhibitor. Nonetheless, this work reinforces the potential of repurposing Tacrine for cancer and enhances the antiproliferative activity of this drug through its conjugation to a CPP.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17