Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis

Weam Siheri; Godwin U. Ebiloma; John O. Igoli; Alexander I. Gray; Marco Biddau; Pilaslak Akrachalanont; Samya Samya Sh M D Alenezi; Mohammad A. Alwashih; RuAngelie Edrada Ebel; Sylke Müller; Catherine E. Lawrence; James Fearnley; David G. Watson; Harry P. De Koning

doi:10.3390/molecules24061041

Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis

Weam Siheri, Godwin U. Ebiloma, John O. Igoli, Alexander I. Gray, Marco Biddau, Pilaslak Akrachalanont, Samya Samya Sh M D Alenezi, Mohammad A. Alwashih, RuAngelie Edrada Ebel, Sylke Müller, Catherine E. Lawrence, James Fearnley, David G. Watson, Harry P. De Koning

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article

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Abstract

Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4’-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.

Original language	English
Article number	1041
Number of pages	12
Journal	Molecules
Volume	24
Issue number	6
DOIs	https://doi.org/10.3390/molecules24061041
Publication status	Published - 15 Mar 2019

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Propolis

Trichinella spiralis

Caenorhabditis elegans

Plasmodium falciparum

isolation

Phospholipids

Trypanocidal Agents

Libya

Foreskin

Methyl Ethers

Trypanosoma brucei brucei

Metabolomics

Helminths

Phytochemicals

Fibroblasts

Choline

Complex Mixtures

Metabolism

Ethanol

Derivatives

Keywords

trypanosoma brucei
bilobol
alkylresorcinol
metabolomics
anthelminthic activity

Cite this

Siheri, W., Ebiloma, G. U., Igoli, J. O., Gray, A. I., Biddau, M., Akrachalanont, P., ... De Koning, H. P. (2019). Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis. Molecules, 24(6), [1041]. https://doi.org/10.3390/molecules24061041

Siheri, Weam ; Ebiloma, Godwin U. ; Igoli, John O. ; Gray, Alexander I. ; Biddau, Marco ; Akrachalanont, Pilaslak ; Samya Sh M D Alenezi, Samya ; Alwashih, Mohammad A. ; Edrada Ebel, RuAngelie ; Müller, Sylke ; Lawrence, Catherine E. ; Fearnley, James ; Watson, David G. ; De Koning, Harry P. / Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis. In: Molecules. 2019 ; Vol. 24, No. 6.

@article{d89ddd2bd3844f85bd545ce00e73b2b5,

title = "Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis",

abstract = "Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4’-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.",

keywords = "trypanosoma brucei, bilobol, alkylresorcinol, metabolomics, anthelminthic activity",

author = "Weam Siheri and Ebiloma, {Godwin U.} and Igoli, {John O.} and Gray, {Alexander I.} and Marco Biddau and Pilaslak Akrachalanont and {Samya Sh M D Alenezi}, Samya and Alwashih, {Mohammad A.} and {Edrada Ebel}, RuAngelie and Sylke M{\"u}ller and Lawrence, {Catherine E.} and James Fearnley and Watson, {David G.} and {De Koning}, {Harry P.}",

year = "2019",

month = "3",

day = "15",

doi = "10.3390/molecules24061041",

language = "English",

volume = "24",

journal = "Molecules",

issn = "1420-3049",

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Siheri, W, Ebiloma, GU, Igoli, JO, Gray, AI, Biddau, M, Akrachalanont, P , Samya Sh M D Alenezi, S, Alwashih, MA, Edrada Ebel, R, Müller, S, Lawrence, CE, Fearnley, J, Watson, DG & De Koning, HP 2019, 'Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis', Molecules, vol. 24, no. 6, 1041. https://doi.org/10.3390/molecules24061041

Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis. / Siheri, Weam; Ebiloma, Godwin U.; Igoli, John O.; Gray, Alexander I.; Biddau, Marco; Akrachalanont, Pilaslak ; Samya Sh M D Alenezi, Samya; Alwashih, Mohammad A.; Edrada Ebel, RuAngelie; Müller, Sylke; Lawrence, Catherine E.; Fearnley, James; Watson, David G.; De Koning, Harry P.

In: Molecules, Vol. 24, No. 6, 1041, 15.03.2019.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Isolation of a novel flavanonol and an alkylresorcinol with highly potent anti-trypanosomal activity from Libyan propolis

AU - Siheri, Weam

AU - Ebiloma, Godwin U.

AU - Igoli, John O.

AU - Gray, Alexander I.

AU - Biddau, Marco

AU - Akrachalanont, Pilaslak

AU - Samya Sh M D Alenezi, Samya

AU - Alwashih, Mohammad A.

AU - Edrada Ebel, RuAngelie

AU - Müller, Sylke

AU - Lawrence, Catherine E.

AU - Fearnley, James

AU - Watson, David G.

AU - De Koning, Harry P.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4’-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.

AB - Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4’-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.

KW - trypanosoma brucei

KW - bilobol

KW - alkylresorcinol

KW - metabolomics

KW - anthelminthic activity

UR - https://www.mdpi.com/journal/molecules

U2 - 10.3390/molecules24061041

DO - 10.3390/molecules24061041

M3 - Article

VL - 24

JO - Molecules

JF - Molecules