PMID: 11328760May 1, 2001Paper

HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans

The Journal of Antimicrobial Chemotherapy
K S ParkY K Paik

Abstract

The antifungal properties of 515 synthetic and semi-synthetic protoberberines were investigated. HWY-289 was chosen for further study because it exhibited the most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate toxicity in rats. HWY-289 inhibited the incorporation of L-[methyl-(14)C]methionine into the C-24 of ergosterol in whole cells of C. albicans (IC(50) 20 microM). However, HWY-289 (100 microM) had no effect on mammalian cholesterol biosynthesis in rat microsomes while miconazole (100 microM) was a potent inhibitor of cholesterol biosynthesis under identical assay conditions. A second major target site for HWY-289 was identified that involves cell wall biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin synthase isozymes CaCHS1 and CaCHS2, with IC(50) values of 22 microM for each enzyme. The effect was highly specific in that HWY-289 had no significant effect on C. albicans CaCHS3 (IC(50) > 200 microM). Thus, HWY-289 compared favourably with well-established antifungal agents as an inhibitor of the growth of Candida species in vitro, and may have considerable potential as a new class of antif...Continue Reading

References

Jan 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A R BowenP W Robbins
Jan 1, 1988·The Journal of Infectious Diseases·J M BeckerF Naider
Jul 26, 1984·Biochimica Et Biophysica Acta·N S Ryder, M C Dupont
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·C E BulawaJ M Becker
Sep 1, 1994·Microbiology·B E CausierD J Adams
Apr 1, 1996·Journal of Bacteriology·T MioH Yamada-Okabe
Sep 19, 1997·Trends in Microbiology·M E KlepserM A Pfaller
May 16, 1998·Trends in Microbiology·A H GrollT J Walsh
Jun 26, 1999·The Journal of Antimicrobial Chemotherapy·K S ParkY K Paik

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Citations

Feb 28, 2006·Revista iberoamericana de micología·Frank C Odds
Mar 4, 2005·Biological & Pharmaceutical Bulletin·Yongmoon Han, Jue-Hee Lee
Feb 16, 2011·Toxicology and Applied Pharmacology·Ga Eun LeeYong-Chul Kim
Jan 8, 2014·Expert Opinion on Therapeutic Patents·María Victoria CastelliSusana A Zacchino
Jan 29, 2011·Archives of Oral Biology·Guo-Xian WeiChristine D Wu
Jan 5, 2017·Journal of Medicinal Chemistry·Shanchao WuChunquan Sheng
Jul 8, 2016·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Y K Shin, K Y Kim
May 30, 2006·Bioorganic & Medicinal Chemistry Letters·Ki Duk ParkSung Uk Kim
Oct 12, 2010·Bioorganic & Medicinal Chemistry Letters·Ki Duk ParkSung Uk Kim
Jul 22, 2020·Journal of Medicinal Chemistry·Wei LiuShengzheng Wang

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