Anti-breast cancer action of carbonic anhydrase IX inhibitor 4-[4-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-benzylidene-hydrazinocarbonyl]-benzenesulfonamide (BSM-0004): in vitro and in vivo studies

被引：13

作者：

Mishra, Chandra Bhushan ^{[1
]}

Mongre, Raj Kumar ^{[2
]}

Prakash, Amresh ^{[3
]}

Jeon, Raok ^{[1
]}

Supuran, Claudiu T. ^{[4
]}

Lee, Myeong-Sok ^{[2
]}

机构：

[1] Sookmyung Womens Univ, Coll Pharm, Cheongpa Ro 47 Gil, Seoul 04310, South Korea

[2] Sookmyung Womens Univ, Cellular Heterogene Res Ctr, Mol Canc Biol Lab, Dept Biosyst, Cheongpa Ro47 Gil, Seoul 04310, South Korea

[3] Amity Univ, Amity Inst Integrat Sci & Hlth, Gurgaon, India

[4] Univ Firenze, Sez Sci Farmaceut & Nutraceut, Dipartimento Neurofarba, I-50019 Florence, Italy

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2021年 / 36卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Human carbonic anhydrase IX; inhibition constant; breast cancer; cancer therapy; cytotoxicity; ANTICONVULSANT ACTION DESIGN; THERAPEUTIC TARGET; RISK-FACTORS; CELLS; XII; BENZENESULFONAMIDES; DERIVATIVES; EXPRESSION; DISCOVERY; APOPTOSIS;

D O I：

10.1080/14756366.2021.1909580

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Anti-breast cancer action of novel human carbonic anhydrase IX (hCA IX) inhibitor BSM-0004 has been investigated using in vitro and in vivo models of breast cancer. BSM-0004 was found to be a potent and selective hCA IX inhibitor with a Ki value of 96 nM. In vitro anticancer effect of BSM-0004 was analysed against MCF 7 and MDA-MA-231 cells, BSM-0004 exerted an effective cytotoxic effect under normoxic and hypoxic conditions, inducing apoptosis in MCF 7 cells. Additionally, this compound significantly regulates the expression of crucial biomarkers associated with apoptosis. The investigation was extended to confirm the efficacy of this hCA IX inhibitor against in vivo model of breast cancer. The results specified that the treatment of BSM-0004 displayed an effective in vivo anticancer effect, reducing tumour growth in a xenograft cancer model. Hence, our investigation delivers an effective anti-breast cancer agent that engenders the anticancer effect by inhibiting hCA IX.

引用

页码：954 / 963

页数：10

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