Design， Synthesis and Anti-cervical Cancer Activity of Piperine-bicycloamide Derivatives

doi:10.7503/cjcu20230520

Chem. J. Chinese Universities ›› 2024, Vol. 45 ›› Issue (4): 20230520.doi: 10.7503/cjcu20230520

• Organic Chemistry • Previous Articles Next Articles

Design， Synthesis and Anti-cervical Cancer Activity of Piperine-bicycloamide Derivatives

WANG Xiujun¹, JIANG Wentao¹, HE Jingliang¹, CHEN Huijie¹, QIAO Yue¹, WANG Dewei², WANG Bingyan¹, HOU Xiao¹, LIU Wei³, GENG Ting¹, ZHANG Siyi¹, LIU Xing¹, MA Shaojie¹(), LIU Bin¹, YANG Mingli⁴(), JI Jing¹()

^1.College of Pharmacy，Jiangsu Ocean University，Lianyungang 222000，China
^2.The 716th Institute of China Shipbuilding Industry Group Co. ，Ltd. ，Lianyungang 222000，China
^3.Lianyungang Economic and Technological Development Zone Life and Health Industry Park Management Office （New Pharmaceutical Industry Development Bureau），Lianyungang 222000，China
^4.Department of Pharmacy，Kangda College of Nanjing Medical University，Lianyungang 222000，China

Received:2023-12-25 Online:2024-04-10 Published:2024-01-31
Contact: MA Shaojie E-mail:msjgdpu@126.com;mingliyang@njmu.edu.cn;jijing@jou.edu.cn
Supported by:
the Open Project of the Key Laboratory of Active Molecular Screening for Marine Drugs in Jiangsu Province, Jiangsu Ocean University, China(HY202302);the Operating Fee of the Key Laboratory of Marine Product Inspection Technology in Lianyungang City, China(5507018036);the Jiangsu Graduate Practice Innovation Program Project, China(SY202352X1)

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Abstract

Abstract:

In this paper， a series of piperine-dicycloamide derivatives was synthesized using piperine as parent nucleus， and their structures were confirmed by means of nuclear magnetic resonance hydrogen spectroscopy （¹H NMR）， nuclear magnetic resonance carbon spectroscopy（¹³C NMR） and high-resolution mass spectrometry（HRMS）. Methyl thiazolyl tetrazolium（MTT） assay showed that these compounds had good inhibitory effects on kidney cells（293T）， cervical cancer（HeLa） and breast cancer（MD-MB-321）. Most derivatives had better inhibitory activity on HeLa cells than positive controls fluorouracil（5-FU）and piperine， and compound 6b had the highest anti-proliferative activity on HeLa cells. The half maximal inhibitory concentration（IC₅₀） of MDA-MB-321 cells was 3.49 μmol/L， and the IC₅₀ of MDA-MB-321 cells was 20.89 μmol/L. The mechanism study showed that compound 6b not only effectively inhibited the migration， invasion， adhesion and cloning ability of HeLa cells， but also showed a strong inhibitory effect on the growth of xenografts of HeLa cells. Therefore， compound 6b has the potential to be a lead compound in tumor therapy.

Key words: Piperine, Anti-tumor, Piperine-bicycloamide derivative

CLC Number:

O626

TrendMD:

WANG Xiujun, JIANG Wentao, HE Jingliang, CHEN Huijie, QIAO Yue, WANG Dewei, WANG Bingyan, HOU Xiao, LIU Wei, GENG Ting, ZHANG Siyi, LIU Xing, MA Shaojie, LIU Bin, YANG Mingli, JI Jing. Design， Synthesis and Anti-cervical Cancer Activity of Piperine-bicycloamide Derivatives[J]. Chem. J. Chinese Universities, 2024, 45(4): 20230520.

Figures/Tables 4

References 26

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Compd.	Structure	IC₅₀/（μmol·L^-1）
Compd.	Structure	293T	HeLa	MDA⁃MB⁃321
2a		>100	26.85±1.65	53.34±9.40
2b		59.44±9.11	21.62±2.18	83.29±26.95
3a		82.28±11.87	51.33±3.44	>100
3b		55.24±2.41	54.34±6.39	44.64±1.85
3c		>100	34.00±1.17	>100
3d		>100	53.23±3.10	>100
3e		>100	79.97±3.58	>100
4a		>100	12.93±0.64	>100
4b		45.22±3.66	24.70±2.57	28.43±3.98
5a		87.35±8.00	4.30±0.12	>100
5b		27.07±1.23	8.59±0.65	>100
6a		41.99±5.80	22.82±0.51	>100
6b		45.34±2.75	3.49±0.42	20.89±0.44
Piperine 5⁃Fu		42.77±7.61	44.03±3.23	239.03±37.49
Piperine 5⁃Fu		107.72±8.92	42.07±0.74	33.79±0.85

Compd.	Structure	IC₅₀/（μmol·L^-1）
Compd.	Structure	293T	HeLa	MDA⁃MB⁃321
2a		>100	26.85±1.65	53.34±9.40
2b		59.44±9.11	21.62±2.18	83.29±26.95
3a		82.28±11.87	51.33±3.44	>100
3b		55.24±2.41	54.34±6.39	44.64±1.85
3c		>100	34.00±1.17	>100
3d		>100	53.23±3.10	>100
3e		>100	79.97±3.58	>100
4a		>100	12.93±0.64	>100
4b		45.22±3.66	24.70±2.57	28.43±3.98
5a		87.35±8.00	4.30±0.12	>100
5b		27.07±1.23	8.59±0.65	>100
6a		41.99±5.80	22.82±0.51	>100
6b		45.34±2.75	3.49±0.42	20.89±0.44
Piperine 5⁃Fu		42.77±7.61	44.03±3.23	239.03±37.49
Piperine 5⁃Fu		107.72±8.92	42.07±0.74	33.79±0.85

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Design， Synthesis and Anti-cervical Cancer Activity of Piperine-bicycloamide Derivatives

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