A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates
Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challen...
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MDPI AG
2024-12-01
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| Series: | Marine Drugs |
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| author | Takahiro Jomori Nanami Higa Shogo Hokama Trianda Ayuning Tyas Natsuki Matsuura Yudai Ueda Ryo Kimura Sei Arizono Nicole Joy de Voogd Yasuhiro Hayashi Mina Yasumoto-Hirose Junichi Tanaka Kanami Mori-Yasumoto |
| author_facet | Takahiro Jomori Nanami Higa Shogo Hokama Trianda Ayuning Tyas Natsuki Matsuura Yudai Ueda Ryo Kimura Sei Arizono Nicole Joy de Voogd Yasuhiro Hayashi Mina Yasumoto-Hirose Junichi Tanaka Kanami Mori-Yasumoto |
| author_sort | Takahiro Jomori |
| collection | DOAJ |
| description | Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against <i>Leishmania major</i> promastigotes, with IC<sub>50</sub> values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL. |
| format | Article |
| id | doaj-art-b785aaec09f448eb812cd3f51b89c9e8 |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-b785aaec09f448eb812cd3f51b89c9e82025-01-24T13:39:28ZengMDPI AGMarine Drugs1660-33972024-12-012311610.3390/md23010016A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine InvertebratesTakahiro Jomori0Nanami Higa1Shogo Hokama2Trianda Ayuning Tyas3Natsuki Matsuura4Yudai Ueda5Ryo Kimura6Sei Arizono7Nicole Joy de Voogd8Yasuhiro Hayashi9Mina Yasumoto-Hirose10Junichi Tanaka11Kanami Mori-Yasumoto12Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, JapanFaculty of Agriculture, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, Miyazaki 889-2192, JapanNaturalis Biodiversity Center, 2300 RA Leiden, The NetherlandsFaculty of Agriculture, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, Miyazaki 889-2192, JapanTropical Technology Plus, Uruma, Okinawa 904-2234, JapanDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, JapanLeishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against <i>Leishmania major</i> promastigotes, with IC<sub>50</sub> values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL.https://www.mdpi.com/1660-3397/23/1/16<i>Leishmania major</i>furanosesterterpenoidtetronic acidγ-butenolidemarine sponge |
| spellingShingle | Takahiro Jomori Nanami Higa Shogo Hokama Trianda Ayuning Tyas Natsuki Matsuura Yudai Ueda Ryo Kimura Sei Arizono Nicole Joy de Voogd Yasuhiro Hayashi Mina Yasumoto-Hirose Junichi Tanaka Kanami Mori-Yasumoto A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates Marine Drugs <i>Leishmania major</i> furanosesterterpenoid tetronic acid γ-butenolide marine sponge |
| title | A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates |
| title_full | A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates |
| title_fullStr | A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates |
| title_full_unstemmed | A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates |
| title_short | A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates |
| title_sort | novel sesterterpenoid petrosaspongin and γ lactone sesterterpenoids with leishmanicidal activity from okinawan marine invertebrates |
| topic | <i>Leishmania major</i> furanosesterterpenoid tetronic acid γ-butenolide marine sponge |
| url | https://www.mdpi.com/1660-3397/23/1/16 |
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