| RRC ID |
74477
|
| 著者 |
Saito S, Funayama K, Kato W, Okuda M, Kawamoto M, Matsubara T, Sato T, Sato A, Otsuguro S, Sasaki M, Orba Y, Sawa H, Maenaka K, Shindo K, Imoto M, Arai MA.
|
| タイトル |
Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses.
|
| ジャーナル |
J Nat Prod
|
| Abstract |
Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations.
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| 巻・号 |
85(11)
|
| ページ |
2583-2591
|
| 公開日 |
2022-11-25
|
| DOI |
10.1021/acs.jnatprod.2c00550
|
| PMID |
36223390
|
| PMC |
PMC9578650
|
| MeSH |
Antiviral Agents* / chemistry
Antiviral Agents* / metabolism
Antiviral Agents* / pharmacology
Azo Compounds* / chemistry
Azo Compounds* / metabolism
Azo Compounds* / pharmacology
COVID-19*
Chlorocebus aethiops
Dogs
HEK293 Cells
Heat-Shock Response
Humans
Influenza A Virus, H1N1 Subtype* / drug effects
Influenza, Human / drug therapy
Madin Darby Canine Kidney Cells
Orthomyxoviridae Infections / drug therapy
SARS-CoV-2* / drug effects
Streptomyces* / chemistry
Streptomyces* / metabolism
Vero Cells
|
| IF |
3.782
|
| リソース情報 |
| ヒト・動物細胞 |
MDCK(RCB0995)
293T(RCB2202) |
