Synthesis of novel SRPK1-targeting hybrid compounds incorporating antimetabolites for cancer therapy
George Leonidis, Ioanna Sigala, Michail Spathakis, George Kolios, Thomas Giannakouros, Eleni Nikolakaki, Vasiliki Sarli
TL;DR
Researchers designed and tested new hybrid compounds that target SRPK1, a protein linked to cancer, and found one compound, geo140, to be particularly effective in inhibiting cancer cell growth.
Contribution
The study introduces hybrid compounds combining SRPK1 inhibitors with antimetabolites, showing enhanced anticancer activity and novel mechanisms.
Findings
Geo140, a hybrid with 5-FU, showed strong SRPK1 inhibition and cytotoxicity in HeLa and K562 cells.
Geo140 increased mitotic cells with accumulated SRPK1, suggesting an effect on cell cycle progression.
Abstract
Serine/arginine protein kinase 1 (SRPK1) plays a pivotal role in the phosphorylation of SR/RS domain-containing proteins, which are involved in various cellular processes. Its overexpression has been associated with the progression of various malignancies, positioning SRPK1 as a promising target for cancer treatment. In this study, we report the design, synthesis, and preliminary biological evaluation of two hybrid molecules, geo15 and geo140, which combine known SRPK1 inhibitors with the antimetabolites gemcitabine and 5-fluorouracil (5-FU), respectively. These conjugates were synthesized to assess whether hybridization enhances potency compared to the parent compounds, and to investigate potential novel mechanisms of action. In vitro assays were performed to evaluate SRPK1 inhibition and antiproliferative activity in selected cancer cell lines. Among the tested compounds, the…
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Taxonomy
TopicsCancer therapeutics and mechanisms · Cancer Treatment and Pharmacology · Bioactive Compounds and Antitumor Agents