Digyaindoleacid A: 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid

Samuel Kwain; Gilbert Mawuli Tetevi; Thomas Mensah; Anil Sazak Camas; Mustafa Camas; Aboagye Kwarteng Dofuor; Faustus Akankperiwen Azerigyik; Hai Deng; Marcel Jaspars; Kwaku Kyeremeh

doi:10.3390/M1080

Digyaindoleacid A: 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid

Samuel Kwain, Gilbert Mawuli Tetevi, Thomas Mensah, Anil Sazak Camas, Mustafa Camas, Aboagye Kwarteng Dofuor, Faustus Akankperiwen Azerigyik, Hai Deng, Marcel Jaspars, Kwaku Kyeremeh^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at t_R ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1, 1 produced a half-maximal inhibitory concentration (IC₅₀) 5.21 µM compared to the standard diminazene aceturate (IC₅₀ = 1.86 µM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC₅₀ = 135.41 µM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

Original language	English
Article number	M1080
Number of pages	10
Journal	MolBank
Volume	2019
Issue number	3
DOIs	https://doi.org/10.3390/M1080
Publication status	Published - 14 Sept 2019

Bibliographical note

Funding Information:
Funding: K.K. wishes to thank the Centre for African Wetlands (CAW), University of Ghana, for providing seed funding to enable the collection of sediments for microbe isolation and The World Academy of Sciences (TWAS) Research Grant Award_17-512 RG/CHE/AF/AC_G. K.K. is also very grateful to the Cambridge-Africa Partnership for Research Excellence (CAPREx), which is funded by the Carnegie Corporation of New York, for a postdoctoral fellowship. K.K. also appreciates the Cambridge–Africa ALBORADA Research Fund for support and the Medical Research Council (MRC)/Department for International Development (DFID) African Research Leaders MR/S00520X/1 Award. S.K. wishes to thank the Carnegie Building a New Generation of Academics (BANGA)-Africa Project Award for a PhD scholarship and M.T. is grateful for an MPhil full scholarship from the TWAS Research Grant Award_17-512 RG/CHE/AF/AC_G.

Keywords

Antileishmanials
Antitrypanosomals
Cell cycle
Cell viability
Leishmaniasis
Spectrometry
Spectroscopy
Trypanosomiasis
Tryptophan

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@article{bda0bc8af0664bb7945c410508111c33,

title = "Digyaindoleacid A: 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid",

abstract = "Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 µM compared to the standard diminazene aceturate (IC50 = 1.86 µM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 µM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).",

keywords = "Antileishmanials, Antitrypanosomals, Cell cycle, Cell viability, Leishmaniasis, Spectrometry, Spectroscopy, Trypanosomiasis, Tryptophan",

author = "Samuel Kwain and Tetevi, {Gilbert Mawuli} and Thomas Mensah and Camas, {Anil Sazak} and Mustafa Camas and Dofuor, {Aboagye Kwarteng} and Azerigyik, {Faustus Akankperiwen} and Hai Deng and Marcel Jaspars and Kwaku Kyeremeh",

note = "Funding Information: Funding: K.K. wishes to thank the Centre for African Wetlands (CAW), University of Ghana, for providing seed funding to enable the collection of sediments for microbe isolation and The World Academy of Sciences (TWAS) Research Grant Award_17-512 RG/CHE/AF/AC_G. K.K. is also very grateful to the Cambridge-Africa Partnership for Research Excellence (CAPREx), which is funded by the Carnegie Corporation of New York, for a postdoctoral fellowship. K.K. also appreciates the Cambridge–Africa ALBORADA Research Fund for support and the Medical Research Council (MRC)/Department for International Development (DFID) African Research Leaders MR/S00520X/1 Award. S.K. wishes to thank the Carnegie Building a New Generation of Academics (BANGA)-Africa Project Award for a PhD scholarship and M.T. is grateful for an MPhil full scholarship from the TWAS Research Grant Award_17-512 RG/CHE/AF/AC_G.",

year = "2019",

month = sep,

day = "14",

doi = "10.3390/M1080",

language = "English",

volume = "2019",

journal = "MolBank",

issn = "1422-8599",

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number = "3",

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TY - JOUR

T1 - Digyaindoleacid A

T2 - 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid

AU - Kwain, Samuel

AU - Tetevi, Gilbert Mawuli

AU - Mensah, Thomas

AU - Camas, Anil Sazak

AU - Camas, Mustafa

AU - Dofuor, Aboagye Kwarteng

AU - Azerigyik, Faustus Akankperiwen

AU - Deng, Hai

AU - Jaspars, Marcel

AU - Kyeremeh, Kwaku

N1 - Funding Information: Funding: K.K. wishes to thank the Centre for African Wetlands (CAW), University of Ghana, for providing seed funding to enable the collection of sediments for microbe isolation and The World Academy of Sciences (TWAS) Research Grant Award_17-512 RG/CHE/AF/AC_G. K.K. is also very grateful to the Cambridge-Africa Partnership for Research Excellence (CAPREx), which is funded by the Carnegie Corporation of New York, for a postdoctoral fellowship. K.K. also appreciates the Cambridge–Africa ALBORADA Research Fund for support and the Medical Research Council (MRC)/Department for International Development (DFID) African Research Leaders MR/S00520X/1 Award. S.K. wishes to thank the Carnegie Building a New Generation of Academics (BANGA)-Africa Project Award for a PhD scholarship and M.T. is grateful for an MPhil full scholarship from the TWAS Research Grant Award_17-512 RG/CHE/AF/AC_G.

PY - 2019/9/14

Y1 - 2019/9/14

N2 - Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 µM compared to the standard diminazene aceturate (IC50 = 1.86 µM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 µM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

AB - Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 µM compared to the standard diminazene aceturate (IC50 = 1.86 µM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain 927/4 GUTat10.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 µM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

KW - Antileishmanials

KW - Antitrypanosomals

KW - Cell cycle

KW - Cell viability

KW - Leishmaniasis

KW - Spectrometry

KW - Spectroscopy

KW - Trypanosomiasis

KW - Tryptophan

UR - http://www.scopus.com/inward/record.url?scp=85075516071&partnerID=8YFLogxK

U2 - 10.3390/M1080

DO - 10.3390/M1080

M3 - Article

AN - SCOPUS:85075516071

SN - 1422-8599

VL - 2019

JO - MolBank

JF - MolBank

IS - 3

M1 - M1080

ER -

Digyaindoleacid A: 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid

Abstract

Bibliographical note

Keywords

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