Synthesis, modification, and biological activity of propargylated methyl dihydroquinopimarates

Abstract The introduction of the alkynyl moiety to the abietane diterpenic core by modification of the cycle E of methyl dihydroquinopimarate is described. The arylpropargyl, aminopropargyl, and 1,2,3-triazole derivatives are synthesized via Sonogashira reaction, Mannich reaction and click-chemistry, correspondingly. The antitumor effect towards the NCI-60 cancer cell line panel and antimicrobial activity against key ESKAPE pathogens of the synthesized compounds were studied in vitro. The cytotoxicity and hemolytic activity of the abietane derivatives was tested using HEK293 human embryonic kidney cell line and the human red blood cells, correspondingly. The methyl dihydroquinopimarate propargyl analogs showed high antitumor activity against leukemia (CCRF-CEM; SR), non-small cell lung cancer (NCI-H522), melanoma (LOX IMVI; MALME-3M), ovarian cancer (IGROV1), and renal cancer (786-0; UO-31) cell lines. The Mannich’s diterpene bases with pyrrolidine and diethylamine fragments exhibited fungicidal activity towards Cr. neoformans (MIC= 16 μg/ml), while possessing low toxicity. The described modifications of the abietane diterpenoids have great potential for further development of new cytotoxic and fungicidal compounds. Graphical Abstract