Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones.
Cryptotanshinone (1), a quinoid diterpene with a nor-abietane skeleton, and three new natural products, 1beta-hydroxycryptotanshinone (2), 1-oxocryptotanshinone (3), and 1-oxomiltirone (4), were isolated from roots of the Iranian medicinal plant Perovskia abrotanoides. Their structures were established using homo- and heteronuclear two-dimensional NMR experiments, supported by HRMS. The total amount of tanshinones isolated from dry roots of Perovskia abrotanoides was about 1.5%. The compounds exhibited leishmanicidal activity in vitro (IC(50) values in the range 18-47 microM). These findings provide a rationale for traditional use of the roots in Iran as a constituent of poultices for treatment of cutaneous leishmaniasis. The isolated tanshinones also inhibited growth of cultured malaria parasites (3D7 strain of Plasmodium falciparum), drug-sensitive KB-3-1 human carcinoma cell line, multidrug-resistant KB-V1 cell line, and human lymphocytes activated with phytohaemagglutinin A (IC(50) values in the range 5-45 microM). The toxicity of tanshinones toward the drug-sensitive KB-3-1 and the multidrug-resistant KB-V1 cells was the same, indicating that the compounds are not substrates for the P-glycoprotein drug efflux pump.
Sairafianpour
M
M
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Christensen
J
J
Staerk
D
D
Budnik
B A
BA
Kharazmi
A
A
Bagherzadeh
K
K
Jaroszewski
J W
JW
D045784:Abietanes; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D006801:Humans; D007492:Iran; D019686:Lamiaceae / Q000737:chemistry*; D018320:Leishmania major / Q000187:drug effects; D008214:Lymphocytes / Q000097:blood / Q000187:drug effects; D019906:Nuclear Magnetic Resonance, Biomolecular; D010616:Phenanthrenes / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D037121:Plant Lectins; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured / Q000187:drug effects
C442705:1-hydroxycryptotanshinone; C442706:1-oxocryptotanshinone; C442707:1-oxomiltirone; D045784:Abietanes; D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D000981:Antiprotozoal Agents; D004224:Diterpenes; D010616:Phenanthrenes; D010835:Phytohemagglutinins; D037121:Plant Lectins; C021751:tanshinone; C037886:cryptotanshinone