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Mar Drugs. 2019 Feb 22;17(2). pii: E133. doi: 10.3390/md17020133.

2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans.

Author information

1
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. hqhqeori@snu.ac.kr.
2
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea. yahyah7@snu.ac.kr.
3
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. beomkoo01@snu.ac.kr.
4
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. eunji525@snu.ac.kr.
5
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. hyunature@snu.ac.kr.
6
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea. shinj@snu.ac.kr.
7
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea. ohkibong@snu.ac.kr.

Abstract

Four 2-alkyl-4-hydroxyquinoline derivatives (14) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans.

KEYWORDS:

2-alkyl-4-hydroxyquinolines; Candida albicans; Streptomyces sp.; cAMP-Efg1 pathway; marine actinomycete; morphogenesis

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