Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety

Abstract

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3c), and [1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3k) displayed better antiproliferative activity with IC50 (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.

Application of triazoles in the structural modification of natural products

“…Dehydroabietic acid-triazole derivatives not only exhibit anti-breast cancer activity 59 but also possess anti-liver cancer activity 69 . A series of dehydroabietic acid-coupled 1,2,3-triazole derivatives was synthesised by Li et al.…”

Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety

“…After treatment for another 48 h and 72 h with different concentrations of the samples (0.8, 4, 20, 100 µM), 20 µL of MTT (5 mg/mL) was added and incubated for about 4 h. The medium was thrown away and the purple formazan precipitations were dissolved in 150 µL DMSO. The O. D. value was measured at 490 nm using an enzyme labeling instrument [24].…”

“…A tetralin derivative 7-isopropyl-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene can be readily prepared from longifolene, which is a major constituent of the abundant and naturally renewable heavy turpentine oil, a by-product in the production of rosin and turpentine from living Pinus. In view of the factors mentioned above, and in continuation of our interest in seeking bioactive compounds from the biological source of natural products [23][24][25][26], a series of novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6-isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1 (2H)-one compounds were designed and synthesized. Additionally, structural characterization and antiproliferative evaluation in vitro against T-24, MCF-7, HepG2, A549, and HT-29 human cancer cell lines for all the target compounds were carried out.…”

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

“…Particularly, it is reported that numerous NO-donating hybrids have the potential to provide novel anticancer candidates with low toxicity and high efficacy against drug-resistant cancers. [22][23][24][25][26][27] Enlightened by these findings, together with our previous studies on the modification of natural products, [28][29][30][31] a modification via integrating DHAA and nitrate pharmacophore into one molecule to generate a novel dehydroabietic acid NO donor hybrids was conducted. The screening of the cytotoxicity of these hybrids against four human cancer cell lines and normal human cell were carried on.…”