Cytotoxic Activities of Amino Acid‐Conjugate Derivatives of Abietane‐Type Diterpenoids against Human Cancer Cell Lines

Abstract

Nine amino acid conjugate derivatives, each 2-10 and 12-20, were prepared from abietic acid (1) and dehydroabietic acid (11), respectively, and they were evaluated for their cytotoxicities against four human cancer cell lines, i.e., leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3). All compounds showed cytotoxicities against HL60 with IC50 values in the range of 2.3-37.3 μM. In addition, most of the derivatives exhibited moderate cytotoxicities against the other cancer cell lines. Among the derivatives, methyl N-[18-oxoabieta-8,11,13-trien-18-yl]-L-tyrosinate (19) exhibited potent cytotoxic activities against four cancer cell lines with IC50 values of 2.3 (HL60), 7.1 (A549), 3.9 (AZ521), and 8.1 μM (SK-BR-3). Furthermore, all derivatives were shown to possess high selective cytotoxic activities for leukemia cells, since they exhibited only weak cytotoxicities against normal lymphocyte cell line RPMI1788.

Antibacterial profiling of abietane-type diterpenoids

“…As a response to the upcoming shortage of potent antibiotics, this study first and foremost aimed to evaluate the antimicrobial potential of amino acid derivatives of abietic acid (1). Although the antiproliferative activity of amino acid-based derivatives of 1 has been previously reported, 17,22 there is yet no detailed study to address their potential antimicrobial properties. Moreover, our previous work showed that the combination of amino acids with an abietane core, such as that of 1a, resulted in potent antimicrobial and anti-biofilm agents, 11,12 which suggests that this type of modification is worth pursuing when designing compounds with potential antimicrobial effects.…”

“…[13][14][15] While 1 itself is not toxic for human cells 14 , several derivatives of 1 and 1a -including some of their amino acid conjugates -exhibit moderate anti-proliferative properties against a panel of tumor cells lines. 16,17 However, their effect on microorganisms has not been elucidated yet. In this paper, we investigated the antibacterial and antifungal properties of a series of abietane derivatives containing amino acid side chains.…”

Diterpenoids of terrestrial origin

“…A series of dehydroabietic acid, dehydroabietylamine and maleopimaric acid derivatives have been synthesized and their activity against human cancer cell lines has been assessed. [87][88][89][90][91] In another study of the abietanes derived from Salvia and Plectranthus species, taxodone (37) proved to be particularly active against human tumour cells. 92 Some tanshinones from S. miltiorrhiza have been shown 93 to inhibit the action of the carboxyesterases in the liver which compromise the activity of pro-drugs, whilst taxusabietane C from Taxus wallichiana is an inhibitor of lipoxygenase.…”

Cytotoxic Constituents from the Sclerotia of Poria cocos against Human Lung Adenocarcinoma Cells by Inducing Mitochondrial Apoptosis

“…Dehydroabietic acid (a naturally occurring diterpene rosin acid) and its synthetic derivatives have exhibited cytotoxicity toward various types of human cancer cells, including lung cancer cells [ 40 , 41 ]. Although the methyl ester derivative of dehydroabietic acid was previously identified in P. cocos and was shown to inhibit the tumor-promoting activity of 12- O -tetradecanoylphorbol-13-acetate (TPA) in vitro [ 42 ], dehydroabietic acid ( 3 ) was isolated from P. cocos and evaluated for its biological effects on human lung cancer cells for the first time in the present study.…”