Structurally Diverse Alkaloids from the Seeds of Peganum harmala

• Published in: Journal of natural products (Washington, D.C.) Vol. 80; no. 2; pp. 551 - 559
• Main Authors: Wang, Kai-Bo, Li, Da-Hong, Bao, Yu, Cao, Fei, Wang, Wen-Jing, Lin, Clement, Bin, Wen, Bai, Jiao, Pei, Yue-Hu, Jing, Yong-Kui, Yang, Danzhou, Li, Zhan-Lin, Hua, Hui-Ming
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 24.02.2017; Amer Chemical Soc
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Carbolines - chemistry; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; HL-60 Cells; Humans; Indole Alkaloids - chemistry; Indole Alkaloids - isolation & purification; Indole Alkaloids - pharmacology; Inhibitory Concentration 50; Life Sciences & Biomedicine; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peganum - chemistry; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; Seeds - chemistry; ELUCIDATION; BETA-CARBOLINE ALKALOIDS; NATURAL-PRODUCTS; DRUGS; ALGORITHM; HARMINE
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b01146

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.