Design, Synthesis and Antitumor Activity of Amino Acid-Modified Pregnane Derivatives

doi:10.6023/cjoc202507006

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (2): 545-553.DOI: 10.6023/cjoc202507006 Previous Articles Next Articles

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氨基酸修饰的孕甾衍生物设计合成及抗肿瘤活性研究

顾运琼^a^,^b, 姚嘉伟^a, 钟智薇^a, 文舒婷^a, 杨坤^c, 刘亚璐^c, 甘春芳^a^,^*()

^a 南宁师范大学化学与材料学院广西天然高分子化学与物理重点实验室广西南宁 530100
^b 玉林师范学院化学与食品科学学院广西农产资源化学与生物技术重点实验室广西玉林 537000
^c 弘瑞药业有限公司山西运城 043600

收稿日期:2025-07-03 修回日期:2025-09-03 发布日期:2025-10-23
通讯作者: 甘春芳
基金资助:
广西自然科学基金(2023GXNSFAA026399); 广西自然科学基金(2023GXNSFDA026063); 国家自然科学基金(22467017); 广西农业资源化学与生物技术重点实验室开放基金(2022KF04); 大学生创新创业训练计划(S202510603146); 大学生创新创业训练计划(S202410603081); 及南宁师范大学教改(2025JGX064)

Design, Synthesis and Antitumor Activity of Amino Acid-Modified Pregnane Derivatives

Yunqiong Gu^a^,^b, Jiawei Yao^a, Zhiwei Zhong^a, Shuting Wen^a, Kun Yang^c, Yalu Liu^c, Chunfang Gan^a^,^*()

^a Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, School of Chemistry and Material, Nanning Normal University, Nanning, Guangxi 530100
^b Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, Yulin, Guangxi 537000
^c Hongrui Pharmaceutical Co., Ltd, Yuncheng, Shanxi 043600

Received:2025-07-03 Revised:2025-09-03 Published:2025-10-23
Contact: Chunfang Gan
Supported by:
Natural Science Foundation of Guangxi(2023GXNSFAA026399); Natural Science Foundation of Guangxi(2023GXNSFDA026063); National Natural Science Foundation of China(22467017); Open Fund of Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology(2022KF04); Innovation and Entrepreneurship Training Program for College Students(S202510603146); Innovation and Entrepreneurship Training Program for College Students(S202410603081); Nanning Normal University Teaching Reform Project(2025JGX064)

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Abstract

The introduction of amino acid fragments into drug molecules represents a significant strategy in the development of novel antitumor agents. This approach serves to overcome the poor solubility and low permeability of the parent drug, thereby enhancing its biological activity. Based on pregnenolone as the lead compound and incorporating structural features of the clinical drug abiraterone, a series of pregnane derivatives bearing various amino acid fragments at the 17-position side chain were designed and synthesized. The in vitro antitumor activities of the target compounds were evaluated using the thiazolyl blue tetrazolium bromide (MTT) assay. The results indicated that when the amino acid fragment existed in the carboxylic acid form, it exhibited negligible inhibitory activity against cancer cells. Conversely, when present in the ester form, it markedly enhanced the antiproliferative effect on cells. Among the synthesized compounds, the L-phenylalanine derivative (7h) demonstrated promising in vitro antiproliferative activity against the SKOV-3 cell line (IC₅₀=15.10 µmol/L). Similarly, the L-deoxyalliin derivative (7d) showed comparable inhibitory activity against the T47D cell line (IC₅₀=15.46 µmol/L). Notably, both compounds 7h and 7d exhibited superior potency compared to the positive control, abiraterone (IC₅₀ values of 59.5 and 34.66 µmol/L against SKOV-3 and T47D, respectively). These findings provide a theoretical foundation and valuable experimental reference for the development of novel anticancer drugs.

Key words: pregnenolone, structure modification, amino acid ester derivative, antiproliferative activity

Cite this article

Yunqiong Gu, Jiawei Yao, Zhiwei Zhong, Shuting Wen, Kun Yang, Yalu Liu, Chunfang Gan. Design, Synthesis and Antitumor Activity of Amino Acid-Modified Pregnane Derivatives[J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 545-553.

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References 16

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Compd.	MCF-7	SKOV-3	T47D	HeLa	293T	Clog P
8a	52.89±1.72	>80	>80	46.74±1.67	>80	2.3
8b	>80	>80	>80	>80	>80	3.7
8c	>80	>80	>80	47.02±1.67	30.29±1.48	4.1
8d	>80	>80	>80	>80	>80	3.74
7a	>80	39.83±10.12	>80	>80	43.28±1.64	2.93
7b	>80	50.89±8.06	>80	45.04±6.66	34.85±4.84	4.31
7c	21.41±0.53	20.38±0.87	21.83±1.34	42.80±1.63	9.46±0.35	4.71
7d	59.35±9.82	20.46±3.15	15.46±1.19	31.57±1.50	12.04±2.28	4.34
7e	60.97±7.61	77.87±0.69	61.99±1.79	>80	24.18±1.97	3.42
7f	24.63±1.39	25.51±4.23	18.80±1.27	71.10±1.85	7.43±3.51	4.65
7g	39.93±4.36	50.55±10.69	35.42±1.55	>80	29.08±0.78	3.76
7h	40.63±5.88	15.10±1.24	>80	25.89±1.41	12.76±1.79	5.1
7i	>80	49.36±3.51	>80	>80	37.84±2.25	2.88
7j	>80	>80	>80	41.93±1.62	37.18±2.54	2.57
Abiraterone	38.20±1.58	59.5±1.77	34.66±1.69	16.86±1.23	>80	5.16

Compd.	MCF-7	SKOV-3	T47D	HeLa	293T	Clog P
8a	52.89±1.72	>80	>80	46.74±1.67	>80	2.3
8b	>80	>80	>80	>80	>80	3.7
8c	>80	>80	>80	47.02±1.67	30.29±1.48	4.1
8d	>80	>80	>80	>80	>80	3.74
7a	>80	39.83±10.12	>80	>80	43.28±1.64	2.93
7b	>80	50.89±8.06	>80	45.04±6.66	34.85±4.84	4.31
7c	21.41±0.53	20.38±0.87	21.83±1.34	42.80±1.63	9.46±0.35	4.71
7d	59.35±9.82	20.46±3.15	15.46±1.19	31.57±1.50	12.04±2.28	4.34
7e	60.97±7.61	77.87±0.69	61.99±1.79	>80	24.18±1.97	3.42
7f	24.63±1.39	25.51±4.23	18.80±1.27	71.10±1.85	7.43±3.51	4.65
7g	39.93±4.36	50.55±10.69	35.42±1.55	>80	29.08±0.78	3.76
7h	40.63±5.88	15.10±1.24	>80	25.89±1.41	12.76±1.79	5.1
7i	>80	49.36±3.51	>80	>80	37.84±2.25	2.88
7j	>80	>80	>80	41.93±1.62	37.18±2.54	2.57
Abiraterone	38.20±1.58	59.5±1.77	34.66±1.69	16.86±1.23	>80	5.16

氨基酸修饰的孕甾衍生物设计合成及抗肿瘤活性研究

Design, Synthesis and Antitumor Activity of Amino Acid-Modified Pregnane Derivatives

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