Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d‑Peptides for Selectively Inhibiting Ovarian Cancer Cells

Cancer is a major public health concern requiring novel
treatment
approaches. Enzyme-instructed self-assembly (EISA) provides a unique
approach for selectively inhibiting cancer cells. However, the structure
and activity correlation of EISA remains to be explored. This study
investigates new EISA substrates of alkaline phosphatase (ALP) to
hinder ovarian cancer cells. Analogues 2–8 were
synthesized by modifying the amino acid residues of a potent EISA
substrate 1 that effectively inhibits the growth of OVSAHO,
a high-grade serous ovarian cancer (HGSOC) cell line. The efficacy
of 2–8 against OVSAHO was assessed, along with
the combination of substrate 1 with clinically used drugs.
The results reveal that substrate 1 displays the highest
cytotoxicity against OVSAHO cells, with an IC50 of around
8 μM. However, there was limited synergism observed between
substrate 1 and the tested clinically used drugs. These
findings indicate that EISA likely operates through a distinct mechanism
that necessitates further elucidation.