Benzoylcyclopropane Derivatives from Hypoxis hemerocallidea Corms

Abstract

Two monobenzoylcyclopropane (hypoxhemerol A (1) and hypoxhemeroloside G (2)) and three dibenzoylcyclopropane (hypoxhemerol B (3), hypoxhemeroloside H (4), and hypoxhemeroloside I (5)) derivatives were isolated from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. This is the first instance where benzoylcyclopropane analogs were isolated from any natural source. Structure elucidation was mainly based on 1D- and 2D-NMR and HRESIMS data. The absolute configuration (2R, 4R) of 1 was determined via NOESY NMR and experimental and calculated ECD data analyses. Compounds 1–5 and 11 recently reported metabolites (hypoxoside, obtuside A, interjectin, acuminoside, curcapicycloside, and hypoxhemerolosides A – F) were screened for in vitro antimicrobial activity against various bacterial and fungal strains. Curcapicycloside and acuminoside exhibited antibacterial activity against Escherichia coli with 78 and 79% inhibition at 20 µg/mL, respectively. Hypoxhemeroloside A showed mild antifungal activity against Cryptococcus neoformans with 63% inhibition at 20 µg/mL.

Key words

Hypoxis hemerocallidea - hypoxidaceae - benzoylcyclopropane - hypoxhemerol - hypoxhemeroloside - antimicrobial

Publikationsverlauf

Eingereicht: 10. Februar 2021

Angenommen nach Revision: 25. Juni 2021

Artikel online veröffentlicht:
30. Juli 2021

• References

• 1 Khan F, Drewes S. The African potato (Hypoxis hemerocallidea): a chemical-historical perspective. S Afr J Sci 2004; 100: 425-430
• 2 Drewes S, Elliot E, Khan F, Dhlamini J, Gcumisa M. Hypoxis hemerocallidea–not merely a cure for benign prostate hyperplasia. J Ethnopharmacol 2008; 119: 593-598
• 3 Owira PM, Ojewole JA. ‘African potato’ (Hypoxis hemerocallidea corm): a plant‐medicine for modern and 21st-century diseases of mankind? A review. Phytother Res 2009; 23: 147-152
• 4 Mofokeng MM, Araya HT, Amoo SO, Sehlola D, du Plooy CP, Bairu MW, Venter S, Mashela PW. Diversity and conservation through cultivation of Hypoxis in Africa–a case study of Hypoxis hemerocallidea . Diversity (Basel) 2020; 12: 122-145
• 5 Van Wyk BE. A broad review of commercially important southern African medicinal plants. J Ethnopharmacol 2008; 119: 342-355
• 6 Grierson D, Afolayan A. An ethnobotanical study of plants used for the treatment of wounds in the Eastern Cape, South Africa. J Ethnopharmacol 1999; 67: 327-332
• 7 Ncube B, Ndhlala AR, Okem A, Van Staden J. Hypoxis (Hypoxidaceae) in African traditional medicine. J Ethnopharmacol 2013; 150: 818-827
• 8 Kabanda MM, Mammino L, Murulana LC, Mwangi HM, Mabusela WT. Antioxidant radical scavenging properties of phenolic pent-4-en-1-yne derivatives isolated from Hypoxis rooperi. A DFT study in vacuo and in solution. Int J Food Prop 2015; 18: 149-164
• 9 Laporta O, Pérez-Fons L, Mallavia R, Caturla N, Micol V. Isolation, characterization and antioxidant capacity assessment of the bioactive compounds derived from Hypoxis rooperi corm extract (African potato). Food Chem 2007; 101: 1425-1437
• 10 Zulfiqar F, Khan SI, Ali Z, Wang YH, Ross SA, Viljoen AM, Khan IA. Norlignan glucosides from Hypoxis hemerocallidea and their potential in vitro anti-inflammatory activity via inhibition of iNOS and NF-κB. Phytochemistry 2020; 172: 112273
• 11 Boukes GJ, van de Venter M, Oosthuizen V. Quantitative and qualitative analysis of sterols/sterolins and hypoxoside contents of three Hypoxis (African potato) spp. Afr J Biotechnol 2008; 7: 1624-1629
• 12 Nair VD, Kanfer I. Sterols and sterolins in Hypoxis hemerocallidea (African potato). S Afr J Sci 2008; 104: 322-324
• 13 Albrecht C, Theron E, Kruger P. Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy. S Afr Med J 1995; 85: 853-860
• 14 Ojewole JA. Antinociceptive, anti-inflammatory and antidiabetic properties of Hypoxis hemerocallidea Fisch. & CA Mey. (Hypoxidaceae) corm [‘African Potato’] aqueous extract in mice and rats. J Ethnopharmacol 2006; 103: 126-134
• 15 Laporta O, Funes L, Garzón MT, Villalaín J, Micol V. Role of membranes on the antibacterial and anti-inflammatory activities of the bioactive compounds from Hypoxis rooperi corm extract. Arch Biochem Biophys 2007; 467: 119-131
• 16 Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA. Anthraquinone-based specialized metabolites from rhizomes of Bulbine natalensis . J Nat Prod 2019; 82: 1893-1901
• 17 Fantoukh OI, Dale OR, Parveen A, Hawwal MF, Ali Z, Manda VK, Khan SI, Chittiboyina AG, Viljoen A, Khan IA. Safety assessment of phytochemicals derived from the globalized South African rooibos tea (Aspalathus linearis) through interaction with CYP, PXR, and P-gp. J Agric Food Chem 2019; 67: 4967-4975
• 18 Majrashi TA, Zulfiqar F, Chittiboyina AG, Ali Z, Khan IA. Isoquinoline alkaloids from Asimina triloba . Nat Prod Res 2019; 33: 2823-2829
• 19 Zulfiqar F, Khan SI, Ross SA, Ali Z, Khan IA. Prenylated flavonol glycosides from Epimedium grandiflorum: cytotoxicity and evaluation against inflammation and metabolic disorder. Phytochem Lett 2017; 20: 160-167
• 20 Fantoukh OI, Albadry MA, Parveen A, Hawwal MF, Majrashi T, Ali Z, Khan SI, Chittiboyina AG, Khan IA. Isolation, synthesis, and drug interaction potential of secondary metabolites derived from the leaves of miracle tree (Moringa oleifera) against CYP3A4 and CYP2D6 isozymes. Phytomedicine 2019; 60: 153010
• 21 Gunasekera SP, Cranick S, Pomponi SA. New sterol ester from a deep water marine sponge, Xestospongia sp. J Nat Prod 1991; 54: 1119-1122
• 22 Rao MR, Faulkner DJ. Clavosolides A and B, dimeric macrolides from the Philippines sponge Myriastra clavosa . J Nat Prod 2002; 65: 386-388
• 23 Steenkamp V, Gouws M, Gulumian M, Elgorashi E, Van Staden J. Studies on antibacterial, anti-inflammatory and antioxidant activity of herbal remedies used in the treatment of benign prostatic hyperplasia and prostatitis. J Ethnopharmacol 2006; 103: 71-75
• 24 Katerere D, Eloff J. Anti-bacterial and anti-oxidant activity of Hypoxis hemerocallidea (Hypoxidaceae): can leaves be substituted for corms as a conservation strategy?. S Afr J Bot 2008; 74: 613-616
• 25 Hutton HM, Schaefer T. Proton coupling constants in substituted cyclopropanes. Can J Chem 1963; 41: 684-689
• 26 Schaefer TP, Hruska F, Kotowycz G. Correlations of proton coupling constants in the cyclopropane ring with electronegativity. Proton resonance spectrum of cyclopropyllithium. Can J Chem 1965; 43: 75-80
• 27 Hutton H, Schaefer T. The proton magnetic resonance spectra of chrysanthemum ethyl ester and the related cis-and trans-chrysanthemumic acids. Can J Chem 1962; 40: 875-881
• 28 CLSI. Reference Method for Broth Dilution antifungal Susceptibility Testing of filamentous Fungi; Approved Standard M38-A2. 2nd edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
• 29 CLSI. Reference Method for Broth Dilution antifungal Susceptibility Testing of Yeasts; Approved Standard M27-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
• 30 CLSI. Methods for Dilution antimicrobial Susceptibility Tests for Bacteria that grow aerobically; Approved Standard M7-A9, 9th edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2012
• 31 Wang YH, Avula B, Fu X, Wang M, Khan IA. Simultaneous determination of the absolute configuration of twelve monosaccharide enantiomers from natural products in a single injection by a UPLC-UV/MS method. Planta Med 2012; 78: 834-837
• 32 Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson RM. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J Clin Microbiol 1998; 36: 362-366
• 33 Wang X, Liu J, Pandey P, Chen J, Fronczek FR, Parnham S, Qi X, Doerksen RJ, Ferreira D, Sun H. Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments. Biochim Biophys Acta Gen Subj 2017; 1861: 3089-3095
• 34 Li F, Pandey P, Janussen D, Chittiboyina AG, Ferreira D, Tasdemir D. Tridiscorhabdin and didiscorhabdin, the first discorhabdin oligomers linked with a direct C–N bridge from the sponge Latrunculia biformis collected from the deep sea in Antarctica. J Nat Prod 2020; 83: 706-713
• 35 Schrödinger Release 2020–4: Maestro version 12.6.144. Schrödinger LLC, New York, NY, 2020. Accessed April 12, 2021 at: https://www.schrodinger.com/downloads/releases?release=561125
• 36 Schrödinger Release 2020–4: LigPrep. Schrödinger LLC, New York, NY, 2020. Accessed April 12, 2021 at: https://www.schrodinger.com/downloads/releases?release=561125
• 37 Schrödinger Release 2020–4: MacroModel. Schrödinger LLC, New York, NY, 2020. Accessed April 12, 2021 at: https://www.schrodinger.com/downloads/releases?release=561125
• 38 Mennucci B, Tomasi J. Continuum solvation models: a new approach to the problem of soluteʼs charge distribution and cavity boundaries. J Chem Phys 1997; 106: 5151-5158
• 39 Li XC, Ferreira D, Ding Y. Determination of absolute configuration of natural products: theoretical calculation of electronic circular dichroism as a tool. Curr Org Chem 2010; 14: 1678-1697
• 40 Autschbach J. Time‐dependent density functional theory for calculating origin‐independent optical rotation and rotatory strength tensors. Chemphyschem 2011; 12: 3224-3235
• 41 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery jr. JA, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 16, Revision B.01. Gaussian, Inc., Wallingford CT, 2016. Accessed April 12, 2021 at: https://gaussian.com/