Antiplasmodial and Antioxidant Isoquinoline Alkaloids from Dehaasia longipedicellata

Abstract

The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).

Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies

“…Two of the compounds, a bisbenzylisoquinoline, (-)-O, O′-dimethylgrisabine (53), and a morphinadienone, (-)-milonine (54), were the most potent compounds, with IC 50 values of 0.031 and 0.097 μM, respectively, which are comparable to the standard, chloroquine (0.090 μM). All of the compounds showed no potency against lung (A549) cancer cells and weak cytotoxicity against skin (A375) cancer cells [44]. Further, two aporphine alkaloids and other compounds were isolated from Xylopia sericea leaves.…”

“…Also, six alkaloids were isolated from Alseodaphne corneri. ese include (+)-laurotetanine (43) and (+)-norstephasubine (44), both of which exhibit strong antiplasmodial activity with IC 50 values of 0.189 and 0.116 μM, respectively [38]. are dimeric.…”

“…Compounds 56-60 were found to exhibit potent inhibitory activity against the growth of P. falciparum 3D7 clone, with IC 50 values of 0.89, 1.49, 1.65, and 2.76 μg/ml, respectively[46]. Compound 60 was previously isolated from Dehaasia longipedicellata but was found to have moderate activity against P. falciparum KI isolate (resistant strain) with IC 50 value of 22.46 μM[44].…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…32 Akihisa et al 33 isolated noroxyhydrastinine Corydalis tomentella [28] 402 Oleracein E Portulaca oleracea [31] 403 Pipermullesine B Piper mullesua [108] 404 Pipermullesine C Piper mullesua [108] 405 Delavatine A Incarvillea delavayi [109] 406 Neotatarine Acorus calamus [110] Cryptocarya griffithiana, and Dehaasia longipedicellata, over the past 5 years. [34][35][36][37][38][39] (+)-N-Methylisococlaurine (24) also was found in Cryptocarya species and (−)-N-methylcoclaurine (25) was identified in the rhizomes of Sinomenium acutum in 2014. 40 Berbithine (26) and 6-( [1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxybenzoic acid methyl ester (27) were isolated from the rhizome of Coptis chinensis.…”

“…40 Berbithine (26) and 6-( [1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxybenzoic acid methyl ester (27) were isolated from the rhizome of Coptis chinensis. 41 In 2018, several benzylisoquinoline alkaloids, including 24, 25, norcolaurine-4′-O-glucoside (28), N-methylhigenamine (29), norcoclaurine-6-O-glucoside (30), norcoclaurine (31), argemexirine (32), lotusine (33), isococlaurine (34), armepavine (35), 6-demethy-4′-methyl-N-methylcoclaurine (36), coclaurine (37), N-nor-O-methylarmepavine (38), isococlaurine-5′-Opentoside (39), and coclaurine-5′-O-pentoside (40) were identified from P. nelumbinis through UPLC-ESI-QTOF-MS. 30 Subsequently, juzirine (41) was identified from the aerial parts of Leonurus japonicus. 42 (R)-(+)-1-Benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (42) from P. oleracea showed anti-inflammatory and β2-adrenergic receptor agonist activities.…”