Structurally Diverse Alkaloids from the Seeds of Peganum harmala

Abstract

Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A–B (1–2); two rare thiazole derivatives, peganumals A–B (3–4); six new β-carboline alkaloids, pegaharmines F–K (5–10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A–B, thiazole fragments in peganumals A–B, and a C-1 α,β-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36–9.25 μM.

Synthesis and Structural Confirmation of the Thiazole Alkaloids Derived from Peganum harmala L.

“…Purification of the residue via flash column chromatography (EtOAc:n-hexane = 1:1) afforded peganumal A (1; 5.4 mg, 89%) as a white solid. The NMR spectra data were consistent with the previously reported [4]. HRMS (FAB) calcd for C 12 H 14 NO 3 S + (M + H + ): 252.0689; found 252.0695; 1 H NMR (500 MHz, DMSO) δ 8.91 (1H, d, J = 0.6 Hz), 8.21 (1H, s), 7.70 (1H, d, J = 0.6 Hz), 6.52 (1H, s), 6.52 (1H, s), 4.08 (2H, s), 3.71 (3H, s), 3.71 (3H, s); 13 C NMR (125 MHz, DMSO) δ 153.1, 148.0, 148.0, 140.5, 139.4, 134.2, 130, 105.9, 105.9, 56.0, 56.0, 31.9.…”

“…According to the synthetic procedure of peganumal A (1), peganumal B (2; 88 mg, 69%) was obtained as a white solid from 11 (176 mg, 0.50 mmol) by using 1 M solution of titanium tetrachloride in methylene chloride (0.75 mL, 0.75 mmol). The NMR spectra data were consistent with the previously reported [4]…”

“…Recently, a Chinese research group isolated the natural thiazole alkaloids peganumal A (1) and B (2) from the seeds of Peganum harmala L. They also evaluated their antiproliferative activities against HL-60, PC-3, and SGC-7901 cancer cell lines, but 1 and 2 did not show significant activities. It was claimed that thiazole was a rarely observed moiety in natural products and was reported for the first time in the genus Peganum [4]. They proposed that 1 and 2 have 2H-thiazole or 2-methylthiazole moieties connected with 4-hydroxy-3,5-dimethoxybenzene by a methylene bridge, respectively (Figure 1).…”

“…Unlike 2, it was difficult to distinguish 1 by two-dimensional NMR studies from its possible regioisomer 1 . Therefore, in the previous paper [4], the structure of peganumal A was not clearly defined and was proposed as 1 via 13 C NMR chemical shift calculations by quantum chemical methods.…”

Antibacterial, Antifungal, Antiviral, and Antiparasitic Activities of Peganum harmala and Its Ingredients: A Review

“…Muhaisen et al [24] observed the in vitro antibacterial (Bacillus cereus ATCC 11778, B. subtilis ATCC 6633, Enterococcus faecalis ATCC 29212, E. coli ATCC 25922, P. aeruginosa Wang et al [18] extracted the seeds of P. harmala with ethanol reflux, adjusted the pH of the extract, extracted it, and passed it through the silica gel column. Six new βCs were identified, i.e., pegaharmines F-K (3-8) (Figure 2).…”