Abstract
Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
| Original language | English |
|---|---|
| Pages (from-to) | 1467-1471 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 23 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2013 Mar 1 |
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Keywords
- Actin
- Actin-depolymerizing activity
- Aplyronine A
- Apoptosis
- Mycalolide B
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
Cite this
Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives. / Ohno, Osamu; Morita, Maho; Kitamura, Kazuhiro; Teruya, Toshiaki; Yoneda, Kozo; Kita, Masaki; Kigoshi, Hideo; Suenaga, Kiyotake.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 5, 01.03.2013, p. 1467-1471.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives
AU - Ohno, Osamu
AU - Morita, Maho
AU - Kitamura, Kazuhiro
AU - Teruya, Toshiaki
AU - Yoneda, Kozo
AU - Kita, Masaki
AU - Kigoshi, Hideo
AU - Suenaga, Kiyotake
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
AB - Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
KW - Actin
KW - Actin-depolymerizing activity
KW - Aplyronine A
KW - Apoptosis
KW - Mycalolide B
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UR - http://www.scopus.com/inward/citedby.url?scp=84873732831&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2012.12.052
DO - 10.1016/j.bmcl.2012.12.052
M3 - Article
VL - 23
SP - 1467
EP - 1471
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 5
ER -