Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds
Jing-Ping Liu,1 Ye-Zhi Xiao,1 Yu Hu,1 Xiao-Nian Li,2 Ming-Jiang Wu,3 Yong Zhao,1 Yan Zhao,1 Ze-Jin Ma,1 Jing Shen11Department of Chemistry, Yunnan Normal University, Kunming 650092, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunmi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2019-08-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/synthesis-and-antitumor-evaluation-of-neolaxiflorin-b-inspired-compoun-peer-reviewed-article-DDDT |
| _version_ | 1811326828222087168 |
|---|---|
| author | Liu JP Xiao YZ Hu Y Li XN Wu MJ Zhao Y Zhao Y Ma ZJ Shen J |
| author_facet | Liu JP Xiao YZ Hu Y Li XN Wu MJ Zhao Y Zhao Y Ma ZJ Shen J |
| author_sort | Liu JP |
| collection | DOAJ |
| description | Jing-Ping Liu,1 Ye-Zhi Xiao,1 Yu Hu,1 Xiao-Nian Li,2 Ming-Jiang Wu,3 Yong Zhao,1 Yan Zhao,1 Ze-Jin Ma,1 Jing Shen11Department of Chemistry, Yunnan Normal University, Kunming 650092, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Kunming 650201, People’s Republic of China; 3Criminal Science and Technology Key Lab of Yunnan Police College, Kunming 650223, People’s Republic of ChinaCorrespondence: Jing-Ping Liu; Jing ShenDepartment of Chemistry, Yunnan Normal University, No. 298, 121st Street, Yunnan, Kunming 650092, People’s Republic of ChinaTel/Fax +86 8 716 513 2144Email Liujp72@163.com shenjingbox0225@hotmail.comBackground: Neolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure–activity relationship studies, the α,β-unsaturated ketone (enone) system is an important active group.Methods: Seven neolaxiflorin B derivatives containing α,β-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay.Results: Compound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells.Conclusion: This study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.Keywords: neolaxiflorin B inspired compounds, unsaturated ketone, antitumor activity |
| first_indexed | 2024-04-13T14:56:11Z |
| format | Article |
| id | doaj.art-78c68d7400694dd9bcce3c2aad1ebabe |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-13T14:56:11Z |
| publishDate | 2019-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-78c68d7400694dd9bcce3c2aad1ebabe2022-12-22T02:42:26ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-08-01Volume 133021302848093Synthesis and antitumor evaluation of neolaxiflorin B inspired compoundsLiu JPXiao YZHu YLi XNWu MJZhao YZhao YMa ZJShen JJing-Ping Liu,1 Ye-Zhi Xiao,1 Yu Hu,1 Xiao-Nian Li,2 Ming-Jiang Wu,3 Yong Zhao,1 Yan Zhao,1 Ze-Jin Ma,1 Jing Shen11Department of Chemistry, Yunnan Normal University, Kunming 650092, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Kunming 650201, People’s Republic of China; 3Criminal Science and Technology Key Lab of Yunnan Police College, Kunming 650223, People’s Republic of ChinaCorrespondence: Jing-Ping Liu; Jing ShenDepartment of Chemistry, Yunnan Normal University, No. 298, 121st Street, Yunnan, Kunming 650092, People’s Republic of ChinaTel/Fax +86 8 716 513 2144Email Liujp72@163.com shenjingbox0225@hotmail.comBackground: Neolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure–activity relationship studies, the α,β-unsaturated ketone (enone) system is an important active group.Methods: Seven neolaxiflorin B derivatives containing α,β-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay.Results: Compound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells.Conclusion: This study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.Keywords: neolaxiflorin B inspired compounds, unsaturated ketone, antitumor activityhttps://www.dovepress.com/synthesis-and-antitumor-evaluation-of-neolaxiflorin-b-inspired-compoun-peer-reviewed-article-DDDTneolaxiflorin B inspired compoundsunsaturated ketoneantitumor activity |
| spellingShingle | Liu JP Xiao YZ Hu Y Li XN Wu MJ Zhao Y Zhao Y Ma ZJ Shen J Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds Drug Design, Development and Therapy neolaxiflorin B inspired compounds unsaturated ketone antitumor activity |
| title | Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds |
| title_full | Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds |
| title_fullStr | Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds |
| title_full_unstemmed | Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds |
| title_short | Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds |
| title_sort | synthesis and antitumor evaluation of neolaxiflorin b inspired compounds |
| topic | neolaxiflorin B inspired compounds unsaturated ketone antitumor activity |
| url | https://www.dovepress.com/synthesis-and-antitumor-evaluation-of-neolaxiflorin-b-inspired-compoun-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT liujp synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT xiaoyz synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT huy synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT lixn synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT wumj synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT zhaoy synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT zhaoy synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT mazj synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds AT shenj synthesisandantitumorevaluationofneolaxiflorinbinspiredcompounds |