Synthesis and Biological Activity of Triterpene–Coumarin Conjugates

Abstract

A set of 12 maslinic acid–coumarin conjugates was synthesized, with 9 being maslinic acid–diamine–coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid–coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC 50 values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 μM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate ( 10 ) showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid–coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.

Nutraceutical Role of Polyphenols and Triterpenes Present in the Extracts of Fruits and Leaves of Olea europaea as Antioxidants, Anti-Infectives and Anticancer Agents on Healthy Growth

“…Several authors have also described both MA and oleanolic acid (OA) and several of their chemical derivatives as effective compounds with antiproliferative and antiviral capacity [ 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ]; moreover, like oleanolic acid, MA and some of its different derivatives possess antibacterial activity [ 103 ] and a potent in vitro AIDS virus protease inhibitory activity [ 104 , 105 , 106 , 132 , 138 , 139 , 140 ]. In this sense, [ 104 ] have shown that MA has a potent inhibitory effect on HIV-1 protease activity and this effect was subsequently corroborated by other groups [ 105 , 138 , 139 , 140 ].…”

Investigation of Novel Mucorales Fungal Inhibitors: Synthesis, In‐Silico Study and Anti‐Fungal Potency of Novel Class of Coumarin‐6‐Sulfonamides‐Thiazole and Thiadiazole Hybrids

“…In ddition to, their potent activity against human fungal pathogens such as C. tropicalis, C. albicans, and Aspergillus fumigatus. [18][19][20] Over the past few years, compounds containing thiazole and/or thiadiazole scaffold are attractive to medicinal chemistry due to their unique chemical properties and diversity of the biological activities. [20][21][22][23][24][25] Therefore, they have therapeutic effects against several diseases such as antimalarial, antimicrobial, antiproliferative agents and anti-inflammatory [26][27][28][29][30] besides their significant with various fungicidal activities .…”

“…The great attention paid by researchers to the study of coumarin derivatives is explained by their broad spectrum of biological activities including anti‐inflammatory, [17] antidiabetic, antiAlzheimer, anticancer, antioxidant, Anticonvulscent, antituberculosis, and as inhibitors of SARS‐CoV‐2 (COVID‐19) virus. In ddition to, their potent activity against human fungal pathogens such as C. tropicalis, C. albicans, and Aspergillus fumigatus [18–20] …”

Are Ancestral Medical Practices the Future Solution to Today’s Medical Problems?

“…Numerous chemical groups are being used in the synthesis of chemical derivatives of the most important triterpenoids in order to select derivatives that present a significant increase in efficiency in their bioactivity. Among them, acyl, aminoacyl, and dipeptidyl groups [ 26 , 27 , 41 , 42 ], pegylated and pegylated diamine derivatives [ 43 , 44 , 45 , 46 ], and even coumarin conjugates [ 47 ] stand out. In all cases, the anticancer, anti-inflammatory, antioxidant, or antiviral effects originally present in the molecules from which they are obtained are significantly increased.…”