Isoprenylated Flavonoids with PTP1B Inhibition from Macaranga denticulata

Abstract

Three new C-methylated and isoprenylated chalcone derivatives, dentichalcones A–C (1–3), together with six known compounds (4–9), were isolated from the twigs and leaves of Macaranga denticulata. Their structures were elucidated by spectroscopic analysis, including 1D, 2D NMR, and MS data. The known compounds, (2E)-1-(5,7-dihydroxy-2,2,6-trimethyl-2H-benzopyran-8-yl)-3-(4-methoxyphenyl)-2-propen-1-one (4), (2E)-1-(5,7-dihydroxy-2,2-dimethyl-2H-benzopyran-8-yl)-3-phenyl-2-propen-1-one (5), laxichalcone (6), macarangin (7), bonanniol A (8), and bonannione A (9), showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) in vitro.Graphical AbstractThree new C-methylated and isoprenylated chalcone derivatives, dentichalcones A–C (1–3), together with six known compounds, were isolated from the twigs and leaves of Macaranga denticulata. Some compounds showed inhibitory activities against PTP1B in vitro.

Phytochemistry and pharmacology of natural prenylated flavonoids

“…374 , 375 , 3′- O -methyl-5′-methoxydiplacone ( 371 ), tomentone ( 408 ), and paulownione C ( 415 ) show inhibitory activities with IC 50 values of 0.05–2.46 µ M. Compounds 374 and 375 both bearing two hydroxy groups on the ring B and an unmodified geranyl side chain showed inhibitory activities against 5-LOX almost 10 times greater than the positive control zileuton (IC 50 value: 0.35 µ M) (Hanáková et al 2017 ). Additionally, 369 also named bonannione A was isolated from Macaranga denticulata (Zhang et al 2016 ). Another study assayed the geranylated flavonoids ( 373 , 379 – 382 , 394–398 , and 400–406 ) from the fruits of Paulownia tomentosa were tested for inhibitory effect on human neutrophil elastase (HNE) in vitro which stimulates the release of inflammatory cytokines such as IL-6, IL-8, and other cytokines, exacerbating the inflammatory process.…”

“…Protein tyrosine phosphatase 1B (PTP1B), a negative regulator in the insulin signaling pathway, was evidenced as a promising drug target for type 2 diabetes. The prenylated flavonoids, macarangin ( 143 ), bonannione A ( 337 ), bonanniol A ( 378 ), (2 E )-1-(5,7-dihydroxy-2,2,6-trimethyl-2 H -benzopyran-8-yl)-3-(4-methoxyphenyl)-2-propen-1-one ( 588 ), (2 E )-1-(5,7-dihydroxy-2,2-dimethyl-2 H -benzopyran-8-yl)-3-phenyl-2-propen-1-one ( 589 ), and laxichalcone ( 656 ), from Macaranga denticulate showed potential inhibitory activities against PTP1B in vitro with an IC 50 value of 22.7, 14.0, 15.2, 48.8, 19.3, and 20.7 µ M, respectively (Zhang et al 2016 ). 166 , cudraflavone C ( 167 ), cudraflavanone D ( 472 ), and euchrestaflavanone C ( 510 ) derived from the roots of Cudrania tricuspidate , showed PTP1B inhibitory activities with IC 50 values of 13.6, 9.4, 5.7, and 12.3 µ M, respectively (Quang et al 2015 ).…”

Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata

“…The leaves or stem water decoctions can be used traditionally for washing wounds and drunk as tonic by women after childbirth [3,4]. (Phupattanapong and Wongprasert 1987;Vo 2012) Previous studies on this species have resulted in the isolation of prenylated flavonoids from the leaves [5], stilbenediterpene heterodimer and prenylated flavonoids from the frond [6], terpenoids from the root [7] and C-methylated and isoprenylated chalcones from the twigs and leaves [8][9][10]. As a part of our study in the search for new anticancer compounds from Vietnamese medicinal plants, the ethyl acetate extract of the fruits of M. denticulata was found to inhibit the growth of KB cancer cell line.…”

“…As a part of our study in the search for new anticancer compounds from Vietnamese medicinal plants, the ethyl acetate extract of the fruits of M. denticulata was found to inhibit the growth of KB cancer cell line. In this paper, we report the isolation and structural elucidation of a new modified geranyl-type side chain substituted flavonoid, 6-(8″-hydroxy-3″,8″-trimethyl-oct-2″-enyl)-kaempferol (1) from the fruits of M. denticulata along with 11 prenylated flavonoids (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), a prenylated stilbene (13), two diterpenoids (14 and 15), a sesquiterpenoid (16), and two triterpenoids (17 and 18) from the fruits of Macaranga denticulata Muell. Arg.…”