Synthesis and in vitro antitumor activity of sulfonamide-substituted dehydroabietyl carbamate derivatives

被引：0

作者：

Wang, Derong ^{[1
]}

Pang, Fuhua ^{[1
]}

Qian, Wei ^{[1
]}

Li, Fangyao ^{[1
]}

机构：

[1] Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Key Laboratory of Medical Biotechnology and Translational Medicine, School of Pharmacy, Guili

来源：

Jingxi Huagong/Fine Chemicals | 2024年 / 41卷 / 11期

关键词：

antitumor activity; apoptosis; carbamates; dehydroabietic acid; dehydroabietinol; drug materials;

D O I：

10.13550/j.jxhg.20230912

中图分类号：

学科分类号：

摘要：

Nineteen kinds of N-(aminosulfonyl)dehydrofirnyl carbamate compounds were synthesized from dehydroabietic acid via reduction, esterification and amination three step reaction, and characterized by FTIR, 1HNMR,13CNMR, and ESI-MS. The antitumor activity of Ⅳa~Ⅳs against T-24, HepG2, MCF-7, MGC-803 and Hela tumor cell lines was evaluated using 5-fluorouracil as positive control by tetramethylazolium salt colorimetric assay, followed by analysis on the preliminary mechanism of N-[(2-bromophenyl)sulfamyl]dehydrofirnyl carbamate (Ⅳ d) via Hoechst-33258 staining, cell colony formation, cell cycle distribution, cell apoptosis and western blot assay. The results showed that some compounds exhibited superior antitumor activity in comparison with positive drugs, with compound Ⅳd displaying the best activity against T-24 cells with a half inhibitory concentration of (14.64±0.46) µmol/L, arresting the cell cycle in the S phase thus significantly inhibiting the growth of T-24 cells. In addition, compound Ⅳd could promote T-24 cells apoptosis through upregulation of proapoptotic ones Bax, Cleaved Caspase9, Cleaved Caspase9 and downregulation of antiapoptotic protein Bcl-2, Caspase3, Caspase9 expression. The introduction of sulfanilamide structure could improve the anti-tumor activity of dehydroabietic acid derivatives. © 2024 Fine Chemicals. All rights reserved.

引用

页码：2493 / 2503

页数：10

共 27 条

[1]

SUNG H, FWELAY J, SIEGEL R L, Et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA: A Cancer Journal for Clinicians, 71, 3, pp. 209-249, (2021)

[2]

COSTANTINO L, BARLOCCO D., Challenges in the design of multitarget drugs against multifactorial pathologies: A new life for medicinal chemistry, Future Medicinal Chemistry, 5, 1, pp. 5-7, (2013)

[3]

GE J F, XIONG X Y, Nanoscale drug delivery systems for multidrug resistance inhibition in cancer therapy, Fine Chemicals, 40, 5, pp. 989-999, (2023)

[4]

GUO M, JIN J, ZHAO D, Et al., Research advances on anti-cancer natural products, Frontiers in Oncology, 12, (2022)

[5]

GE J M, LIU Z, ZHONG Z C, Et al., Natural terpenoids with anti-inflammatory activities: Potential leads for anti-inflammatory drug discovery, Bioorganic Chemistry, 124, (2022)

[6]

CHABAN M F, I ANTONIOU A, KARAGIANNI C, Et al., Synthesis and structure-activity relationships of novel abietane diterpenoids with activity against staphylococcus aureus, Future Medicinal Chemistry, 11, 24, pp. 3109-3124, (2019)

[7]

KIM E, KANG Y G, KIM Y J, Et al., Dehydroabietic acid suppresses inflammatory response via suppression of Src-, Syk-, and TAK1-mediated pathways, International Journal of Molecular Sciences, 20, 7, (2019)

[8]

TAO P, WU C Y, HAO J, Et al., Antifungal application of rosin derivatives from renewable pine resin in crop protection, Journal of Agricultural and Food Chemistry, 68, 14, pp. 4144-4154, (2020)

[9]

KOVALEVA K S, YAROVAYA O I, SHEMYUKOV A V, Et al., Synthesis of new heterocyclic dehydroabietylamine derivatives and the FTIR biological activity, Chemistry of Heterocyclic Compounds, 53, pp. 364-370, (2017)

[10]

LU Z, LIU C X, YU X, Et al., Synthesis and anti-free radical activities of several novel derivatives of dehydroabietylamine, Chinese Journal of Organic Chemistry, 33, 3, pp. 562-567, (2013)

← 1 2 3 →