Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis
Tóm tắt
Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2–6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC50 values ranging from 0.002 to 0.91 μM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC50 = 1.80 μM). Among them, cucurbitacin E (IC50 = 0.002 μM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.
Tài liệu tham khảo
El-Hussein A, Manoto SL, Ombinda-Lemboumba S, Alrowaili ZA, Mthunzi-Kufa P. A review of chemotherapy and photodynamic therapy for lung cancer treatment. Anti-Cancer Agents Med Chem. 2021;21:149–61.
Du J, Li J, Gao M, Guan Q, Liu T, Wu Y, Li Z, Zuo D, Zhang W, Wu Y. MAY, a novel tubulin inhibitor, induces cell apoptosis in A549 and A549/Taxol cells and inhibits epithelial-mesenchymal transition in A549/Taxol cells. Chem Biol Interact. 2020;323:109074.
Wang Y, Gilbert MG, Mathew B, Brickell CD, Nevling LI. Thymelaeaceae. In: Wu Z-Y, Raven PH, Hong D-Y, editors. Flora of China, vol. 13. Beijing: Science Press & Missouri Botanical Garden Press; 2007. p. 213–50.
Li W, Chen H-Q, Wang H, Mei W-L, Dai H-F. Natural products in agarwood and Aquilaria plants: chemistry, biological activities and biosynthesis. Nat Prod Rep. 2021;38:528–65.
Mei W-L, Lin F, Dai H-F. GC-MS analysis of volatile constituents from flowers and fruits of Aquilaria sinensis. J Trop Subtrop Bot. 2009;17:305–8.
Chu C-W, Li W-J, Li H-T, Huang J-C, Chung M-I, Chen C-Y. Flavonoids from the flowers of Aquilaria sinensis. Chem Nat Compd. 2016;52:497–8.
Yuan H, Zhao J, Wang M, Khan SI, Zhai C, Xu Q, Huang J, Peng C, Xiong G, Wang W. Benzophenone glycosides from the flower buds of Aquilaria sinensis. Fitoterapia. 2017;121:170–4.
Zhang X, Li H, Wang W, Chen T, Xuan L. Lipid-lowering activities of cucurbitacins isolated from Trichosanthes cucumeroides and their synthetic derivatives. J Nat Prod. 2020;83(12):3536–44.
Jacobs H, Singh T, Reynolds WF, McLean S. Isolation and 13C-NMR assignments of cucurbitacins from Cayaponia angustiloba, Cayaponia racemosa, and Gurania subumbellata. J Nat Prod. 1990;53:1600–5.
Ryu SY, Lee SH, Choi SU, Lee CO, No Z, Ahn JW. Antitumor activity of Trichosanthes kirilowii. Arch Pharm Res. 1994;17:348–53.
Maatooq G, El-Sharkawy S, Afifi MS, Rosazza JPN. Microbial transformation of cucurbitacin E 2-O-β-D-glucopyranoside. J Nat Prod. 1995;58:165–71.
Valdés E, González C, Díaz K, Vásquez-Martínez Y, Mascayano C, Torrent C, Cabezas F, Mejias S, Montoya M, Martín C-S, Muñoz MA, Joseph-Nathan P, Osorio M, Taborga L. Biological properties and absolute configuration of flavanones from Calceolaria thyrsiflora Graham. Front Pharmacol. 2020;11:1125.
Wu B, Kwon SW, Hwang GS, Park JH. Eight new 2-(2-phenylethyl)chromone (= 2-(2-phenylethyl)-4H-1-benzopyran-4-one) derivatives from Aquilaria malaccensis agarwood. Helv Chim Acta. 2012;95:1657–65.
Mei W-L, Lin F, Zuo W-J, Wang H, Dai H-F. Cucurbitacins from fruits of Aquilaria sinensis. Chin J Nat Med. 2012;10:234–7.
Zhang X, Tao M-H, Chen Y-C, Gao X-X, Tan Y-Z, Zhang W-M. Five cucurbitacins from Aquilaria sinensis peels and their cytotoxic activities. Nat Prod Res Dev. 2014;26:354–7.
Silva IT, Carvalho A, Lang KL, Dudek SE, Masemann D, Duran FJ, Caro MSB, Rapp UR, Wixler V, Schenkel EP, Simões CMO, Ludwig S. In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B. PLoS ONE. 2015;10:e0117794.
Yang J, Su Y, Luo J-F, Gu W, Niu H-M, Li Y, Wang Y-H, Long C-L. New amide alkaloids from Piper longum fruits. Nat Prod Bioprospect. 2013;3:277–81.
Wei S-Y, Hu D-B, Xia M-Y, Luo J-F, Yan H, Yang J-H, Wang Y-S, Wang Y-H. Sesquiterpenoids and 2-(2-phenylethyl)chromone derivatives from the resinous heartwood of Aquilaria sinensis. Nat Prod Bioprosp. 2021;11:545–55.