New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685
Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (<b>1</b>), β-resoantarctines A-C (<b>3</b>, <b>5</b>, <b>6</b>) and 8-dehydro-β-resoantarctine A (<b>4</b>), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (&l...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/21/3/178 |
| _version_ | 1797610517024473088 |
|---|---|
| author | Elena V. Leshchenko Alexandr S. Antonov Gleb V. Borkunov Jessica Hauschild Olesya I. Zhuravleva Yuliya V. Khudyakova Alexander S. Menshov Roman S. Popov Natalya Yu Kim Markus Graefen Carsten Bokemeyer Gunhild von Amsberg Anton N. Yurchenko Sergey A. Dyshlovoy |
| author_facet | Elena V. Leshchenko Alexandr S. Antonov Gleb V. Borkunov Jessica Hauschild Olesya I. Zhuravleva Yuliya V. Khudyakova Alexander S. Menshov Roman S. Popov Natalya Yu Kim Markus Graefen Carsten Bokemeyer Gunhild von Amsberg Anton N. Yurchenko Sergey A. Dyshlovoy |
| author_sort | Elena V. Leshchenko |
| collection | DOAJ |
| description | Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (<b>1</b>), β-resoantarctines A-C (<b>3</b>, <b>5</b>, <b>6</b>) and 8-dehydro-β-resoantarctine A (<b>4</b>), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (<b>2</b>), were isolated from the ethyl acetate extract of the fungus <i>Penicillium antarcticum</i> KMM 4685 associated with the brown alga <i>Sargassum miyabei</i>. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds <b>3</b>–<b>6</b> were proposed. For the very first time, the relative configuration of the C-14 center of a known compound <b>2</b> was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites <b>3</b>–<b>6</b> were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds <b>3</b>, <b>4</b> and <b>5</b> exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells. |
| first_indexed | 2024-03-11T06:16:20Z |
| format | Article |
| id | doaj.art-7a45f1d52cd346fba6773655d5a9d784 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-11T06:16:20Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-7a45f1d52cd346fba6773655d5a9d7842023-11-17T12:17:38ZengMDPI AGMarine Drugs1660-33972023-03-0121317810.3390/md21030178New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685Elena V. Leshchenko0Alexandr S. Antonov1Gleb V. Borkunov2Jessica Hauschild3Olesya I. Zhuravleva4Yuliya V. Khudyakova5Alexander S. Menshov6Roman S. Popov7Natalya Yu Kim8Markus Graefen9Carsten Bokemeyer10Gunhild von Amsberg11Anton N. Yurchenko12Sergey A. Dyshlovoy13G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaMartini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, RussiaDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, GermanyFive new β-resorcylic acid derivatives, 14-hydroxyasperentin B (<b>1</b>), β-resoantarctines A-C (<b>3</b>, <b>5</b>, <b>6</b>) and 8-dehydro-β-resoantarctine A (<b>4</b>), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (<b>2</b>), were isolated from the ethyl acetate extract of the fungus <i>Penicillium antarcticum</i> KMM 4685 associated with the brown alga <i>Sargassum miyabei</i>. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds <b>3</b>–<b>6</b> were proposed. For the very first time, the relative configuration of the C-14 center of a known compound <b>2</b> was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites <b>3</b>–<b>6</b> were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds <b>3</b>, <b>4</b> and <b>5</b> exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.https://www.mdpi.com/1660-3397/21/3/178marine-derived fungussecondary metabolites<i>Penicillium antarcticum</i>p-glycoprotein inhibitory activityprostate cancerβ-resorcylic acid |
| spellingShingle | Elena V. Leshchenko Alexandr S. Antonov Gleb V. Borkunov Jessica Hauschild Olesya I. Zhuravleva Yuliya V. Khudyakova Alexander S. Menshov Roman S. Popov Natalya Yu Kim Markus Graefen Carsten Bokemeyer Gunhild von Amsberg Anton N. Yurchenko Sergey A. Dyshlovoy New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 Marine Drugs marine-derived fungus secondary metabolites <i>Penicillium antarcticum</i> p-glycoprotein inhibitory activity prostate cancer β-resorcylic acid |
| title | New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 |
| title_full | New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 |
| title_fullStr | New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 |
| title_full_unstemmed | New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 |
| title_short | New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus <i>Penicillium antarcticum</i> KMM 4685 |
| title_sort | new bioactive β resorcylic acid derivatives from the alga derived fungus i penicillium antarcticum i kmm 4685 |
| topic | marine-derived fungus secondary metabolites <i>Penicillium antarcticum</i> p-glycoprotein inhibitory activity prostate cancer β-resorcylic acid |
| url | https://www.mdpi.com/1660-3397/21/3/178 |
| work_keys_str_mv | AT elenavleshchenko newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT alexandrsantonov newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT glebvborkunov newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT jessicahauschild newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT olesyaizhuravleva newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT yuliyavkhudyakova newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT alexandersmenshov newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT romanspopov newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT natalyayukim newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT markusgraefen newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT carstenbokemeyer newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT gunhildvonamsberg newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT antonnyurchenko newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 AT sergeyadyshlovoy newbioactivebresorcylicacidderivativesfromthealgaderivedfungusipenicilliumantarcticumikmm4685 |