Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia, and synthesis and structure-activity relationships of related compounds

  • Bioorg Med Chem. 2014 Jan 1;22(1):269-76. doi: 10.1016/j.bmc.2013.11.032.
Yumin Dai  1 ,  Liva Harinantenaina  1 ,  Jessica D Bowman  2 ,  Isabel Osorio Da Fonseca  2 ,  Peggy J Brodie  1 ,  Michael Goetz  3 ,  Maria B Cassera  2 ,  David G I Kingston  4
Affiliations
  • 1. Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
  • 2. Department of Biochemistry and the Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.
  • 3. Natural Products Discovery Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
  • 4. Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States. Electronic address: [email protected].
PMID: 24326280 DOI: 10.1016/j.bmc.2013.11.032
Abstract

Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new Anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6-9). The structures of the two new compounds were elucidated based on analyses of their 1D and 2D NMR spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the strongest antiplasmodial activity among all the isolated compounds, with IC₅₀ values of 0.4 ± 0.1 and 0.2 ± 0.1 μM, respectively. The two new compounds displayed modest activities, with IC₅₀ values of 26 ± 4 and 9 ± 1 μM, respectively. Due to the synthetic accessibility of the new compounds and the increased activity shown by the dimeric compounds, a structure-activity relationship study was conducted. As a result, one analogue of kniphofione B (4), the caffeic acid derivative of aloe-emodin, was found to have the highest activity among all the aloe-emodin derivatives, with an IC50 value of 1.3 ± 0.2 μM.

Keywords
Anthraquinone; Antiplasmodial acitivity; BVTJETXSTYXTDR-VOTSOKGWSA-N; BXWGUDGILDGCGB-UHFFFAOYSA-N; CUKVWNAGSQVAJV-UHFFFAOYSA-N; DBAJNFVKBYXSGU-DUXPYHPUSA-N; DDXMLLFCNJDJDZ-FNORWQNLSA-N; DVLGUQIRWOBEAE-UHFFFAOYSA-N; DZIWALDLFXZKAP-VQHVLOKHSA-N; FSQDQCKBPJZGSC-RMKNXTFCSA-N; FUECAILUKAJTBR-UHFFFAOYSA-N; GJDUVVABRMOOQT-UHFFFAOYSA-N; HLOQRMGUBNDJOS-MDZDMXLPSA-N; HOVDZHKFZHIEPB-UHFFFAOYSA-N; IZDBQZFKJYYUGE-MDZDMXLPSA-N; JNAZKJLAUIOKDJ-UHFFFAOYSA-N; KCZMHHVFUMWLAY-RMKNXTFCSA-N; KSTMMFCURGNHNW-UHFFFAOYSA-N; Kniphofia ensifolia; LQGUBLBATBMXHT-UHFFFAOYSA-N; MSPWCCZZOGHZHE-UHFFFAOYSA-N; NRVKYGSWTHZIQC-UHFFFAOYSA-N; PCJVJTNTIXLPGR-UHFFFAOYSA-N; RJHCHYHEHFGDLC-JXMROGBWSA-N; ROHPHZDISZCEMO-UHFFFAOYSA-N; Structure–activity relationship; UMHLRYWUBPIPAY-JXMROGBWSA-N; WPPHHEBOIPHPLG-VQHVLOKHSA-N; YDQWDHRMZQUTBA-UHFFFAOYSA-N; YRUMLFPFVRGJGH-UHFFFAOYSA-N; YXSQXZFTAVZWMO-BQYQJAHWSA-N; ZRRZSYXEHVZHQQ-UHFFFAOYSA-N.