Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2946-2952. doi: 10.1016/j.bmcl.2017.05.006.

Manh Tuan Ha ¹, Manh Hung Tran ², Thien Thuong Phuong ³, Jeong Ah Kim ⁴, Mi Hee Woo ⁵, Jae Sue Choi ⁶, Suhyun Lee ⁷, Jeong Hyung Lee ⁸, Hyeong Kyu Lee ⁹, Byung Sun Min ¹⁰

Affiliations

1 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea; Department of Bioactive Products, Institute of Marine Biochemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay District, Hanoi, Viet Nam.
2 Biomedical Science Department, VNUK Institute for Research and Executive Education, The University of Danang, 158A Le Loi, Hai Chau District, Danang City, Viet Nam.
3 National Institute of Medicinal Materials, 3B Quang Trung Street, Hanoi, Viet Nam.
4 College of Pharmacy, Kyungpook National University, Daegu 702-701, Republic of Korea.
5 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
6 Faculty of Food Science and Biotechnology, Pukyung National University, Busan 608-737, Republic of Korea.
7 College of Natural Science, Kangwon National University, Kangwon 200-701, Republic of Korea.
8 College of Natural Science, Kangwon National University, Kangwon 200-701, Republic of Korea. Electronic address: jhlee36@kangwon.ac.kr.
9 Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, Chungbuk 363-883, Republic of Korea.
10 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea. Electronic address: bsmin@cu.ac.kr.

PMID: 28506750 DOI: 10.1016/j.bmcl.2017.05.006

Abstract

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine Diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known Diterpenoids (4-5, 8-13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in vitro against three non-small cell lung Cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC₅₀ values between 0.4μM and 5.9μM. Erythroformine B (7) significantly induced Apoptosis in all three Cancer cells in a concentration-dependent manner.

Keywords

Apoptosis; Cassaine diterpene alkaloid; Erythrophleum fordii; Non-small cell lung cancers (NSCLC).

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