Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium

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

doi:10.3390/M1094

Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium

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

^*Corresponding author for this work

Research output: Contribution to journal › Comment/debate › peer-review

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Abstract

The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at t_R ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC₅₀ = 115.41 and 28.75 µM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

Original language	English
Article number	M1094
Number of pages	9
Journal	MolBank
Volume	2019
Issue number	4
DOIs	https://doi.org/10.3390/M1094
Publication status	Published - 21 Nov 2019

Keywords

Alkaloid
Antileishmanials
Antitrypanosomals
Imidazole
Leishmaniasis
Paenibacillus
Trypanosomiasis

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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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@article{3acb62eda9ee49b88e0e6fbb9320866f,

title = "Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium",

abstract = "The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 µM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.",

keywords = "Alkaloid, Antileishmanials, Antitrypanosomals, Imidazole, Leishmaniasis, Paenibacillus, Trypanosomiasis",

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

note = "Author Contributions: K.K. and H.D. collected mangrove sediments and isolated the strain DE2SH. A.S.C. and M.C. identified the exact taxonomy of the strain after K.K. isolated DNA and whole genome sequenced the strain. M.J. and H.D. provided access to facilities for mass spectrometry and data interpretation. K.K. performed chemical profiling to identify the major metabolites. S.K., G.M.T. and T.M. performed seed culture, large scale culture, isolation and purification of compound. K.K. measured all NMR, IR and UV, analyzed the results and integration of data to give the complete structure of the compound. K.K., S.K. and G.M.T. wrote the initial draft of the article which was edited and finalized by all the authors. Funding: KK wishes to thank the Centre for African Wetlands (CAW), University of Ghana, for providing seed funding to enable the collection of soil samples for microbe isolation and a 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. K.K., H.D. and M.J. are grateful for this research which is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID African Research Leaders Award (MR/S00520X/1). S.K. wishes to thank the Carnegie BANGA-Africa Project Award for a PhD scholarship and M.T. is grateful for an MPhil full scholarship from TWAS Research Grant Award_17-512 RG/CHE/AF/AC_G. Acknowledgments: All the authors extend their gratitude to the Department of Chemistry, UG for providing NMR facility. Conflicts of Interest: The authors declare no conflicts of interests",

year = "2019",

month = nov,

day = "21",

doi = "10.3390/M1094",

language = "English",

volume = "2019",

journal = "MolBank",

issn = "1422-8599",

publisher = "MDPI AG",

number = "4",

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TY - JOUR

T1 - Paenidigyamycin g

T2 - 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium

AU - Tetevi, Gilbert Mawuli

AU - Kwain, Samuel

AU - Mensah, Thomas

AU - Camas, Anil Sazak

AU - Camas, Mustafa

AU - Dofuor, Aboagye Kwarteng

AU - Azerigyik, Faustus Akankperiwen

AU - Oluwabusola, Emmanuel

AU - Deng, Hai

AU - Jaspars, Marcel

AU - Kyeremeh, Kwaku

N1 - Author Contributions: K.K. and H.D. collected mangrove sediments and isolated the strain DE2SH. A.S.C. and M.C. identified the exact taxonomy of the strain after K.K. isolated DNA and whole genome sequenced the strain. M.J. and H.D. provided access to facilities for mass spectrometry and data interpretation. K.K. performed chemical profiling to identify the major metabolites. S.K., G.M.T. and T.M. performed seed culture, large scale culture, isolation and purification of compound. K.K. measured all NMR, IR and UV, analyzed the results and integration of data to give the complete structure of the compound. K.K., S.K. and G.M.T. wrote the initial draft of the article which was edited and finalized by all the authors. Funding: KK wishes to thank the Centre for African Wetlands (CAW), University of Ghana, for providing seed funding to enable the collection of soil samples for microbe isolation and a 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. K.K., H.D. and M.J. are grateful for this research which is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID African Research Leaders Award (MR/S00520X/1). S.K. wishes to thank the Carnegie BANGA-Africa Project Award for a PhD scholarship and M.T. is grateful for an MPhil full scholarship from TWAS Research Grant Award_17-512 RG/CHE/AF/AC_G. Acknowledgments: All the authors extend their gratitude to the Department of Chemistry, UG for providing NMR facility. Conflicts of Interest: The authors declare no conflicts of interests

PY - 2019/11/21

Y1 - 2019/11/21

N2 - The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 µM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

AB - The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 µM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

KW - Alkaloid

KW - Antileishmanials

KW - Antitrypanosomals

KW - Imidazole

KW - Leishmaniasis

KW - Paenibacillus

KW - Trypanosomiasis

UR - http://www.scopus.com/inward/record.url?scp=85075528182&partnerID=8YFLogxK

U2 - 10.3390/M1094

DO - 10.3390/M1094

M3 - Comment/debate

AN - SCOPUS:85075528182

VL - 2019

JO - MolBank

JF - MolBank

SN - 1422-8599

IS - 4

M1 - M1094

ER -

Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium

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Keywords

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