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,~(13)C 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 IC_(50)(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.
NSTL
Mdpi