2-Amino-nonyl-6-methoxyl-tetralin muriate inhibits sterol C-14 reductase in the ergosterol biosynthetic pathway.

Acta Pharmacologica Sinica
Rong-mei LiangYuan-ying Jiang

Abstract

To investigate the action mechanism of a novel chemical structural aminotetralin derivate, 2-Amino-Nonyl-6-Methoxyl-Tetralin Muriate (10b), against Candida albicans (C albicans) in the ergosterol biosynthetic pathway. Antifungal susceptibility test of 10b was carried out using broth microdilution method, the action mechanism of 10b against C albicans was investigated by GC-MS spectrometry and real-time RT-PCR assay, and cytotoxicity of 10b in vitro was assessed by MTS/PMS reduction assay. 10b reduced the ergosterol content markedly, and the 50% ergosterol content inhibitory concentration (ECIC(50) value) was 0.08 microg/mL. Although the sterol composition of 10b-grown cells was completely identical with that of erg24 strain, the content of ergosta-8,14,22-trienol in 10b-grown cells was much higher than that in erg24 strain. Real-time RT-PCR assay revealed a global upregulation of sterol metabolism genes. In addition, the 50% inhibitory concentration (IC(50) value) of 10b was 11.30 microg/mL for murine embryonic fibroblasts and 35.70 microg/mL for human normal liver cells. 10b possessed a mode of action different from that of azoles and morpholines, whose targets were sterol C-14 reductase (encoded by ERG24 gene) and sterol C-5 ...Continue Reading

References

Jun 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·G DixonP Broad
May 17, 2001·Antimicrobial Agents and Chemotherapy·M D De BackerH Vanden Bossche
Jul 29, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Luis Ostrosky-ZeichnerStuart H Cohen
Apr 12, 2005·Applied Microbiology and Biotechnology·A LemkeO Kayser
Apr 14, 2006·Journal of Medicinal Chemistry·Chunquan ShengJiaguo Lü
Mar 22, 2007·Biochemical and Biophysical Research Communications·Sandeep Shrivastava, Amitabha Chattopadhyay
Sep 29, 2007·Journal of Medicinal Chemistry·Bin YaoHui Tang
Feb 27, 2008·The Journal of Cell Biology·Hui JinEric Grote
Feb 6, 2009·Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology·Yukio OkuKoji Yokoyama
May 2, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xian-Jun QuShu-Xiang Cui

❮ Previous
Next ❯

Citations

Nov 22, 2013·PloS One·Lan-Xue ZhaoYuan-Ying Jiang
Dec 24, 2013·Future Medicinal Chemistry·Nicolas DelattinKarin Thevissen
Dec 1, 2015·ACS Medicinal Chemistry Letters·Gorakhnath R JachakD Srinivasa Reddy
Oct 11, 2017·Molecular & Cellular Proteomics : MCP·Kristina PoljakMarkus Aebi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.