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 journalComment/debate

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.

Original languageEnglish
Article numberM1094
Number of pages9
JournalMolBank
Volume2019
Issue number4
DOIs
Publication statusPublished - 21 Nov 2019

Fingerprint

Antiparasitic Agents
imidazoles
Paenibacillus
Trypanosoma brucei brucei
broths
bioassay
alkaloids
macrophages
metabolites
International System of Units
activity (biology)
toxicity
bacteria
mice
Leishmania donovani
screening
Bioassay
Macrophages
selectivity
Nucleic Acid Databases

Keywords

  • Alkaloid
  • Antileishmanials
  • Antitrypanosomals
  • Imidazole
  • Leishmaniasis
  • Paenibacillus
  • Trypanosomiasis

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Tetevi, G. M., Kwain, S., Mensah, T., Camas, A. S., Camas, M., Dofuor, A. K., ... Kyeremeh, K. (2019). Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium. MolBank, 2019(4), [M1094]. https://doi.org/10.3390/M1094

Paenidigyamycin g : 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium. / Tetevi, Gilbert Mawuli; Kwain, Samuel; Mensah, Thomas; Camas, Anil Sazak; Camas, Mustafa; Dofuor, Aboagye Kwarteng; Azerigyik, Faustus Akankperiwen; Oluwabusola, Emmanuel; Deng, Hai; Jaspars, Marcel; Kyeremeh, Kwaku.

In: MolBank, Vol. 2019, No. 4, M1094, 21.11.2019.

Research output: Contribution to journalComment/debate

Tetevi, GM, Kwain, S, Mensah, T, Camas, AS, Camas, M, Dofuor, AK, Azerigyik, FA, Oluwabusola, E, Deng, H, Jaspars, M & Kyeremeh, K 2019, 'Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium', MolBank, vol. 2019, no. 4, M1094. https://doi.org/10.3390/M1094
Tetevi GM, Kwain S, Mensah T, Camas AS, Camas M, Dofuor AK et al. Paenidigyamycin g: 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium. MolBank. 2019 Nov 21;2019(4). M1094. https://doi.org/10.3390/M1094
Tetevi, Gilbert Mawuli ; Kwain, Samuel ; Mensah, Thomas ; Camas, Anil Sazak ; Camas, Mustafa ; Dofuor, Aboagye Kwarteng ; Azerigyik, Faustus Akankperiwen ; Oluwabusola, Emmanuel ; Deng, Hai ; Jaspars, Marcel ; Kyeremeh, Kwaku. / Paenidigyamycin g : 1-acetyl-2,4-dimethyl-3-phenethyl-1H-imidazol-3-ium. In: MolBank. 2019 ; Vol. 2019, No. 4.
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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 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.",
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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",
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AU - Tetevi, Gilbert Mawuli

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AU - Mensah, Thomas

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AU - Camas, Mustafa

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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

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