Abstract
BackgroundEthnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum.MethodsThe column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P. barbatum, the isolated compounds (1–3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity.ResultsThree dihydrobenzofuran derivatives (1–3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 μM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1, 13.4 ± 1.1 and 57.7 ± 0.3 μM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS).ConclusionBased on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.
Highlights
Polygonum barbatum is a perennial herb, mostly found in shady and marshy places near river banks, ponds and other aquatic areas in different countries of SouthEast Asia [25, 26]
The ultravoilet visible spectroscopy (UV) spectrum showed absorption bands at λmax 306 (2.4) and 220 (3.4) nm while infrared spectroscopy (IR) spectrum showed absorption at 3036, 2810, 1734, 1440, 1204 cm−1 suggesting the presence of alkene, ester, and alkyl aryl ether moiety
Two doublets for other aromatic protons were revealed in 1H-nuclear magnetic resonance spectroscopy (NMR) spectrum at δH 6.80 (d, J = 1.8 Hz, H-2′, 1H), δH 6.61 (d, J = 8.2 Hz, H-5′, 1H,) while doublet of doublet was observed for proton at δH 6.63
Summary
Polygonum barbatum is a perennial herb, mostly found in shady and marshy places near river banks, ponds and other aquatic areas in different countries of SouthEast Asia [25, 26]. Various species of Polygonaceae family are used for the management of cardiovascular diseases, hypertension and cancer [14, 29]. Based on the ethnomedicinal background, some species have been verified scientifically for the management of cancer [1, 2, 4, 17]. In indigenous system of medicine, it has been used as potential anticancer agent against oral cancer [18]. P. barbatum has been reported to have antimicrobial activity, suggesting it to be a source of potential antibiotic agents [18]. The family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum
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