Antitumor Agents. 239. Isolation, Structure Elucidation, Total Synthesis, and Anti-Breast Cancer Activity of Neo-tanshinlactone from Salvia miltiorrhiza

Abstract

Neo-tanshinlactone (1) was isolated and synthesized for the first time and evaluated in vitro against several human cancer cell lines. Compound 1 showed significant inhibition against two ER+ human breast cancer cell lines and was 10-fold more potent and 20-fold more selective as compared to tamoxifen citrate. Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer cell line. Therefore, this novel compound merits further development as an anti-breast cancer drug candidate.

Discovery of new anticancer agents from higher plants

“…Compound 38 can sensitize DU-345 breast cancer cells by suppressing the expression of the apoptosis inhibitory protein, Bcl-2 (110). Neo-tanshinlactone ( 39 ) is a new lead antineoplastic compound isolated from S. miltiorrhiza by Dr. Kuo-Hsiung Lee’s research group at the University of North Carolina (111). Unlike the tanshinones, neo-tanshinlactone ( 39 ) possesses a lactone feature rather than an ortho -quinone moiety in ring C. This compound exhibited selectivity against two estrogen receptor-positive (ER + ) breast cancer cell lines, MCF-7 and ZR-75-1, with ED 50 values, in turn, of 0.6 and 0.3 μg/mL (111).…”

“…Neo-tanshinlactone ( 39 ) is a new lead antineoplastic compound isolated from S. miltiorrhiza by Dr. Kuo-Hsiung Lee’s research group at the University of North Carolina (111). Unlike the tanshinones, neo-tanshinlactone ( 39 ) possesses a lactone feature rather than an ortho -quinone moiety in ring C. This compound exhibited selectivity against two estrogen receptor-positive (ER + ) breast cancer cell lines, MCF-7 and ZR-75-1, with ED 50 values, in turn, of 0.6 and 0.3 μg/mL (111). Compound 40 , a synthetic analogue of neo-tanshinlactone ( 39 ), was found to inhibit the growth of the estrogen-dependent breast cancer cells, ZR-75-1, in an in vivo xenograft model (112).…”

Synthesis, antitumor activity, and mechanism of action of 6-acrylic phenethyl ester-2-pyranone derivatives

“…Lactone ring systems are found in many bioactive natural products obtained from plants, animals, marine organisms, bacteria, and insects, 10 including those that exhibit various pharmacological activities, such as HIV protease inhibitory, 11 anticonvulsant, 12 antimicrobial, 13 antitumor, 14,15 and other effects. Examples include styryl-2-pyrone, 16 isorumbrin, 17 bufadienolide, 18 neo-tanshinlactone, 19 wortmannin, 20 and camptothecin, 21 as shown in Figure 2. Based on numerous modification studies, such as those performed on camptothecin and its derivatives, a lactone ring can be an important pharmacophore in anticancer drugs.…”

Two Diterpenoids and a Cyclopenta[c]pyridine Derivative from Roots of Salvia digitaloids

“…The diterpenoid constituents of this genus are of great interest due to their diverse structures and significant biological activities [7,8,9]. We previously reported a new antitumor agent, neo-tanshinlactone, which was isolated from Salvia miltiorrhiza [9], and several notable new abietane diterpene alkaloids from Salvia yunnanensis [10]. …”