Computer-aided discovery and biological characterization of human lactate dehydrogenase 5 inhibitors with anti-osteosarcoma activity

Bioorg Med Chem Lett. 2018 Jul 15;28(13):2229-2233. doi: 10.1016/j.bmcl.2018.05.052.

Wei Cao ¹, Le Fang ², Siyong Teng ³, Hongwei Chen ⁴, Zhan Wang ⁵

Affiliations

1 Clinical Laboratory of Beijing Rehabilitation Hospital of Capital Medical University, Xixia Zhuang, Bada Chu, Shijingshan District, Beijing, China.
2 Department of Blood Transfusion, 521 Hospital of Ordnance Industry, Xi'an, China.
3 National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, China.
4 Shanghai Songjiang District Central Hospital, Yuanzhong Road, Songjiang District, Shanghai, China.
5 Department of Orthopaedics, Gansu Provincial Hospital, Lanzhou, Gansu, China. Electronic address: Zhanwang_lanzhou@yeah.net.

PMID: 29861142 DOI: 10.1016/j.bmcl.2018.05.052

Abstract

Human Lactate Dehydrogenase 5 (hLDH5) is overexpressed in various tissues of human tumors, which could be a potential therapeutic target for Cancer treatment. Herein, we describe the computer-aided discovery and biological characterizations of hLDH5 inhibitors with anti-osteosarcoma activity. Biochemical assay indicated that the identified compounds 3 and 9 strongly inhibited hLDH5 function with EC₅₀ values of 0.67 and 0.39 µM, respectively. The MTT assay revealed that most of the identified inhibitors had little effect on MG-63 cell proliferation at 4 µM, only 9 reduced the Cancer cell proliferation at the same concentration, with an IC₅₀ value of 3.18 µM. Our data suggested that 9 could be a starting lead of developing potent hLDH5 inhibitor for the anti-osteosarcoma agents in Cancer treatment.

Keywords

Anticancer drug; Cancer metabolism; Metabolic reprogramming; Proliferation; Virtual screening.

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