title: Identification of anti-HIV active dicaffeoylquinic- and tricaffeoylquinic acids in Helichrysum populifolium by NMR-based metabolomic guided fractionation.
abstract: South Africa being home to more than 35% of the world's Helichrysum species (c.a. 244) of which many are used in traditional medicine, is seen potentially as a significant resource in the search of new anti-HIV chemical entities. It was established that five of the 30 Helichrysum species selected for this study had significant anti-HIV activity ranging between 12 and 21 μg/mL (IC50) by using an in-house developed DeCIPhR method on a full virus model. Subsequent toxicity tests also revealed little or no toxicity for these active extracts. With the use of NMR-based metabolomics, the search for common chemical characteristics within the plant extract was conducted, which resulted in specific chemical shift areas identified that could be linked to the anti-HIV activity of the extracts. The NMR chemical shifts associated with the activity were identified to be 2.56-3.08 ppm, 5.24-6.28 ppm, 6.44-7.04 ppm and 7.24-8.04 ppm. This activity profile was then used to guide the fractionation process by narrowing down and focusing the fractionation and purification processes to speed up the putative identification of five compounds with anti-HIV activity in the most active species, Helichrysum populifolium. The anti-HIV compounds identified for the first time from H. populifolium were three dicaffeoylquinic acid derivatives, i.e. 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid as well as two tricaffeoylquinic acid derivatives i.e. 1,3,5-tricaffeoylquinic acid and either 5-malonyl-1,3,4-tricaffeoylquinic or 3-malonyl-1,4,5-tricaffeoylquinic acid, with the latter being identified for the first time in the genus.
authors.affiliation: Department of Plant Science, University of Pretoria, Pretoria, Gauteng 0002, South Africa.
authors.forename: Heino Martin
authors.initials: HM
authors.lastname: Heyman
authors.affiliation: Department of Plant Science, University of Pretoria, Pretoria, Gauteng 0002, South Africa.
authors.forename: François
authors.initials: F
authors.lastname: Senejoux
authors.affiliation: Department of Biomedicine, University of Basel, Petersplatz 10, 4003 Basel, Switzerland.
authors.forename: Isabell
authors.initials: I
authors.lastname: Seibert
authors.affiliation: Department of Biomedicine, University of Basel, Petersplatz 10, 4003 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.affiliation: Department of Chemistry, University of Pretoria, Pretoria, Gauteng 0002, South Africa.
authors.forename: Vinesh Jaichand
authors.initials: VJ
authors.lastname: Maharaj
authors.affiliation: Department of Plant Science, University of Pretoria, Pretoria, Gauteng 0002, South Africa. Electronic address: marion.meyer@up.ac.za.
authors.forename: Jacobus Johannes Marion
authors.initials: JJ
authors.lastname: Meyer
mesh_terms: D019380:Anti-HIV Agents / Q000302:isolation & purification*; D005591:Chemical Fractionation; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification; D057809:HEK293 Cells; D006678:HIV / Q000187:drug effects; D006367:HeLa Cells; D036562:Helichrysum / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D010936:Plant Extracts; D002726:Chlorogenic Acid; C478100:3,4-di-O-caffeoylquinic acid; C100434:3,5-dicaffeoylquinic acid
keywords: Anti-HIV; Asteraceae; Chlorogenic acid; DeCIPhR; Helichrysum; NMR-based metabolomics