Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid

Abstract

Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

“…[1] Dehydroabietic acid (DHAA) is a natural occurring diterpenic resin acid which can be easily obtained from Pinus rosin or from commercial disproportionated rosin. [2] DHAA and its derivatives exhibited extensive pharmaceutical activities, such as antitumor, [3][4][5][6][7] antimicrobial, [8][9][10] antiprotozoal, [11] antiviral, [12] antifungal, [13][14] gastroprotective, [15] insecticidal [16] anti-inflammatory [17] antiulcer, [18] and anxiolytic [19] activities. Furthermore, DHAA was reported to show properties of enhancing the inhibitory activity of an anticancer drug in cervical carcinoma cells, hepatocellular carcinoma cells, or breast cancer cells.…”

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties

“…Dehydroabietic acid (DHAA) is a naturally occurring tricyclic diterpenic resin acid and can be easily isolated from pinus rosin or disproportionate rosin. DHAA and its derivatives have been reported to have a wide range of biological activities, such as antibacterial [ 4 , 5 ], antiviral [ 6 ], insecticidal [ 7 ], antifungal [ 8 ], anti-aging [ 9 ], antiprotozoal [ 10 ] and anti-inflammatory activity [ 11 ]. In particular, previous research has shown that a large number of DHAA derivatives possess a variety of anticancer activities in many human cancers, and could act at various stages of tumor development to inhibit tumor cell proliferation, as well as to induce tumor cell apoptosis [ 12 , 13 , 14 , 15 ].…”

Synthesis, in vitro Antimicrobial, and Cytotoxic Activities of New 1,3,4‐Oxadiazin‐5(6H)‐one Derivatives from Dehydroabietic Acid

“…Its derivatives have drawn much attention for their broad spectrum of biological activities, including antimicrobial, antiprotozoal, antitumor, antiviral, anti-aging, gastroprotective, antifeedant, and BK-channel opening activities. [6][7][8][9][10][11][12][13] These results suggest that DAA is a promising starting material for the discovery of new antimicrobial or anticancer agents.…”