10.6084/M9.FIGSHARE.18130678
Qian-Qian He
Qian-Qian
He
Yu-Qing Man
Yu-Qing
Man
Kun-Lai Sun
Kun-Lai
Sun
Li-Juan Yang
Li-Juan
Yang
Yan Wu
Yan
Wu
Jing Du
Jing
Du
Wei-Wei Chen
Wei-Wei
Chen
Juan-Juan Dai
Juan-Juan
Dai
Na Ni
Na
Ni
Shuang Miao
Shuang
Miao
Kai-Kai Gong
Kai-Kai
Gong
Aaptamine derivatives with CDK2 inhibitory activities from the South China Sea sponge <i>Aaptos suberitoides</i>
<p>Three new aaptamines (<b>1–3</b>) together with two known derivatives (<b>4–5</b>) were isolated from the South China Sea sponge <i>Aaptos suberitoides</i>. The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds <b>3–5</b> showed moderate cytotoxicities against H1299 and H520 cells with IC<sub>50</sub> values ranging from 12.9 to 20.6 μg/mL. Besides, compounds <b>3–5</b> also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC<sub>50</sub> values of 14.3, 3.0 and 6.0 μg/mL, respectively. In addition, compounds <b>3–5</b> significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound <b>3</b> could effectively bind with CDK2 protein and protect it from the degradation by pronase.</p>
Biochemistry
Pharmacology
Environmental Sciences not elsewhere classified
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Cancer
Inorganic Chemistry
Taylor & Francis
2022
2022-01-10
2024-03-21
Journal contribution
1965194 Bytes
10.1080/14786419.2021.2024533
CC BY 4.0