Leishmanicidal, Antiplasmodial, and Cytotoxic Activity of Novel Diterpenoid 1,2-Quinones from Perovskia abrotanoides:  New Source of Tanshinones

Abstract

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.

Semisynthesis of Isetexane Diterpenoid Analogues and Their Cytotoxic Activity

“…1) In our studies on the chemical constituents of the aerial parts of this plant, purchased from Kordes Jungpflanzen (Germany) (place of produce not specified), we could not obtain tanshinones, and instead, we isolated carnosic acid and demethylsalvicanol (1) (Fig. 1) along with small amounts of rosmanols and carnosols.…”

“…Silica gel column chromatography of a hot EtOAc extract of air dried aerial parts of Perovskia abrotanoides gave demethylsalvicanol (1). The absolute configuration of 1 was reported to be 5S and 10S by Gonzalez et al, on the basis of chemotaxonomic consideration.…”

“…2) Of them, demethylsalvicanol (1), having a rearranged 9 (10 →20)-abeoabietane skeleton, was found to be very rich in the plants (ca. 0.37% yield).…”

Total synthesis of 1-oxomiltirone via Suzuki coupling

“…9 Furthermore, the additional application could synthesize miltirone by the reduction of the ketone group in 6, 5 de-methylation of the methyl ether and the subsequent Dess-Martin oxidation. 4 In conclusion, we have developed a short synthesis route to versatile intermediate 6 via Suzuki coupling as a key reaction.…”

Quinone Derivatives by Chemical Transformations of 16-Hydroxycarnosol from Salvia Species

“…[7][8][9] Tanshinones exhibit a variety of biological activities, 10) including effects on cardiac function, [11][12][13] antioxidant activity, 14,15) aldose reductase inhibitory activity, 16) interactions with the benzodiazepine receptor, 17,18) cytotoxicity, [19][20][21][22] apoptosis induction 23,24) and, in a recent work, leishmanicidal and antiplasmodial activities. 25) The diterpenoid tanshinones have attracted particular attention from medicinal chemists and clinicians due to their interesting physiologic properties, variety of biological activities, and naturally occurrence. [26][27][28] Over 50 tanshinones have so far been identified in Salvia species.…”