Absolute configuration of nafuredin, a new specific NADH-fumarate reductase inhibitor

Takano, Daisuke; Nagamitsu, Tohru; Ui, Hideaki; Shiomi, Kazuro; Yamaguchi, Yuuichi; Masuma, Rokuro; Kuwajima, Isao; Ōmura, Satoshi

doi:10.1016/s0040-4039(01)00355-0

Cited by 33 publications

(20 citation statements)

References 8 publications

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“…All inhibitory activities against nematode complex I (IC 50 values) in Tables 1 and 2 were the average of three independent experiments. 3,123.4,62.7,59.2,35.7,30.9,25.0,18.3,16.2,HRMS (FAB, [M+H] + calcd for C 13 H 29 O 2 Si 245.192713 H 29 O 2 Si 245. , found 245.1931.…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…Nafuredin (1) [1][2][3] was isolated from the fermentation broth of the fungal strain Aspergillus niger FT-0554 while screening for selective complex I inhibitors and proved to be a potent and selective inhibitor against nematode complex I. In addition, 1 demonstrated anthelmintic activity against Haemonchus contortus during in vivo trials with sheeps.…”

Section: Introductionmentioning

confidence: 99%

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Development of a new air-stable structure-simplified nafuredin-γ analog as a potent and selective nematode complex I inhibitor

et al. 2017

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Nafuredin-γ, obtained from natural nafuredin, has demonstrated a potent and selective inhibitory activity against nematode complex I. However, nafuredin-γ is unstable in air since its conjugated dienes are oxygen-labile. The instability in air was naturally solved by the synthesis of structure-simplified nafuredin-γ analogs without conjugated dienes. However, these modified analogs showed lower complex I inhibitory activities. Therefore, new air-stable structure-simplified nafuredin-γ analogs were designed and synthesized herein. Among all analogs synthesized, the one bearing a unique 1-azabicyclo[3.1.0]hexane scaffold showed the highest inhibitory activity (IC 50 = 170 nM) while presenting high selectivity against nematode complex I.

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Section: Enzyme Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a new air-stable structure-simplified nafuredin-γ analog as a potent and selective nematode complex I inhibitor

et al. 2017

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“…(µM) Argifin (6) Argadin (7) Since the inhibition of 7 against Serratia chitinase B was very strong and that of 6 was very weak, we compared crystal structures of Serratia chitinase B-complexed with 6 and 7 [27]. It is known that Asp142, Glu144, and Tyr214 are involved in the catalytic action at the active center of the Serratia chitinase B.…”

Section: Chitinase Inhibitorsmentioning

confidence: 99%

“…The structure of 1 was elucidated by NMR studies as (6E,8E,12E,14E)-3,4-epoxy-2-hydroxy-4,10,12,16-tetramethyl-6,8,12,14-octadecatetraeno-5-lactone [5]. The relative configuration was shown by the nuclear Overhauser effect (NOE) study, and the absolute configuration was elucidated by comparison of the degradation products of 1 and the corresponding synthetic compounds [6].…”

Section: Introductionmentioning

confidence: 99%

Discovery, chemistry, and chemical biology of microbial products

Ōmura

Shiomi

2007

Pure and Applied Chemistry

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Our long-standing and continual screening of microorganisms, especially for antiparasitic agents, has produced a wide variety of compounds of global importance, such as the avermectins. Recent discoveries include nafuredin, atpenins, argifin, and argadin. Nafuredin is a helminth-specific inhibitor of electron-transport enzyme, complex I, which exhibits anthelmintic activity against Haemonchus contortus in sheep. The atpenins are the most potent complex II inhibitors ever reported. Co-crystallization study of atpenin A5 and E. coli complex II indicated the binding mechanism of ubiquinone to complex II. Argifin and argadin are the first cyclic peptides to inhibit chitinase at low concentration. Though structurally similar, their chitinase inhibition mechanisms are quite different.

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“…Its structure is an epoxy-d-lactone with a methylated olefinic side chain [7]. The absolute configuration of 1 was elucidated by comparing ozonolysis products of 1 and their corresponding synthetic compounds [8], and total synthesis of 1 has been also achieved [9].…”

Section: Introductionmentioning

confidence: 99%

A γ-Lactone Form Nafuredin, Nafuredin-γ, also Inhibits Helminth Complex I

Shiomi

Suzuki

et al. 2005

J Antibiot

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Nafuredin, a d -lactone antibiotic, is a fungal metabolite showing selective helminth NADH-fumarate reductase inhibition, and whose target had been revealed as complex I. We found that nafuredin is easily converted to nafuredin-g by weak alkaline treatment. The structure of nafuredin-g was elucidated as a g -lactone form of nafuredin with keto-enol tautomerism. Nafuredin-g shows similar complex I inhibitory activity as nafuredin, and it also possesses anthelmintic activity in vivo.

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Absolute configuration of nafuredin, a new specific NADH-fumarate reductase inhibitor

Cited by 33 publications

References 8 publications

Development of a new air-stable structure-simplified nafuredin-γ analog as a potent and selective nematode complex I inhibitor

Development of a new air-stable structure-simplified nafuredin-γ analog as a potent and selective nematode complex I inhibitor

Discovery, chemistry, and chemical biology of microbial products

A γ-Lactone Form Nafuredin, Nafuredin-γ, also Inhibits Helminth Complex I

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