NQO1-Responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell-Targeted Migrastatic
Artikel i vetenskaplig tidskrift, 2025

Migrastatic drugs targeting cell motility and suppressing invasiveness of solid tumors, have the potential to bring about a paradigm shift in the treatment of solid cancer. Cytochalasin B (CB) is a potent migrastatic compound, but its clinical use is limited by poor selectivity. Here, a NQO1-responsive prodrug, BQTML-CB is developed, synthesized in three steps from cytochalasin B derived from Preussia similis G22. BQTML-CB is selectively activated in NQO1-positive cancer cells, releasing active CB. In vitro, BQTML-CB significantly inhibits proliferation and migration in NQO1-positive U-2OS cells, causing actin disruption and cytokinesis abnormalities, while sparing NQO1-negative B16-F1 cells. The prodrug shows reduced effects on human neutrophils, indicating reduced immunosuppressive activity of BQTML-CB compared to CB. Co-culture studies reveal a beneficial bystander effect, as cleaved CB diffused into adjacent NQO1-deficient cells. These findings support BQTML-CB as a cancer-targeted prodrug with selective antiproliferative and migrastatic properties, highlighting the potential of C7-OH-modified cytochalasans in cancer therapy.

prodrugs

NQO1

cytochalasin B

migrastatics

Författare

Mervic D. Kagho

Göteborgs universitet

Katharina Schmidt

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Christopher Lambert

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Technische Universität Braunschweig

Lili Jia

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Vignesh Venkatakrishnan

Chalmers, Life sciences, Kemisk biologi

Luisa Mehr

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Johan Bylund

Göteborgs universitet

Klemens Rottner

Technische Universität Braunschweig

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Marc Stadler

Technische Universität Braunschweig

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Theresia E. B. Stradal

Helmholtz-Gemeinschaft Deutscher Forschungszentren

Philipp Klahn

Göteborgs universitet

Small

1613-6810 (ISSN) 1613-6829 (eISSN)

Vol. In Press

Ämneskategorier (SSIF 2025)

Molekylärbiologi

Farmakologi och toxikologi

DOI

10.1002/smll.202410861

PubMed

40095397

Relaterade dataset

NQO1-responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell-targeted Migrastatic #NMRXIV:P77 [dataset]

DOI: https://doi.org/10.57992/nmrxiv.p77

Mer information

Senast uppdaterat

2025-04-03