Scopus
YÖKSİS Eşleşti
Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer
Journal of Biomolecular Structure and Dynamics · Ocak 2024
YÖKSİS Kayıtları
Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer
Journal of Biomolecular Structure and Dynamics · 2023 SCI
PROFESÖR SERDAR KARAKURT →
Makale Bilgileri
DergiJournal of Biomolecular Structure and Dynamics
Yayın TarihiOcak 2024
Cilt / Sayfa42 · 8638-8659
Scopus ID2-s2.0-85168896529
Özet
Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors. Communicated by Ramaswamy H. Sarma.
Yazarlar (17)
1
Dimitrios Diamantis
2
Antonios D. Tsiailanis
3
Christina Papaemmanouil
4
Maria Christina Nika
5
Zoi Kanaki
6
Simona Golic Grdadolnik
7
Andrej Babic
8
Eleftherios Paraskevas Tzakos
9
Isabelle Fournier
10
Michel Salzet
11
Prem Prakash Kushwaha
12
Nikolaos S. Thomaidis
13
Theodoros Rampias
14
Eswar Shankar
15
Serdar Karakurt
16
Sanjay Gupta
17
Andreas G. Tzakos
ORCID: 0000-0001-6391-0288
Anahtar Kelimeler
Alkaline phosphatase (ALP)
ALP inhibition
apigenin
cancer
natural products
self-immolative
Kurumlar
Biomedical Research Foundation Academy of Athens
Athens Greece
CASE School of Medicine
Cleveland United States
Institut Universitaire de France
Paris France
National and Kapodistrian University of Athens
Athens Greece
National Institute of Chemistry Ljubljana
Ljubljana Slovenia
Selçuk Üniversitesi
Selçuklu Turkey
Université de Genève
Geneva Switzerland
Université de Lille
Lille France
University of Ioannina
Ioannina Greece
Metrikler
2
Atıf
17
Yazar
6
Anahtar Kelime