Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid

Abstract

Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and therapeutic value. In the present study, we discuss how these compounds are utilized to develop bioactive hybrid compounds that are intended to target cancer cells. Using a bifunctional linker, succinic acid, to combine curcumin and triterpenoic oleanolic acid, several hybrid compounds were prepared. Their cytotoxicity against different cancer cell lines was evaluated and compared with the activity of curcumin (the IC50 value (24 h), for MCF7, HeLaWT and HT-29 cancer cells for KS5, KS6 and KS8 compounds was in the range of 20.6–94.4 µM, in comparison to curcumin 15.6–57.2 µM). Additionally, in silico studies were also performed. The computations determined the activity of the tested compounds towards proteins selected due to their similar binding modes and the nature of hydrogen bonds formed within the cavity of ligand−protein complexes. Overall, the curcumin-triterpene hybrids represent an important class of compounds for the development of effective anticancer agents also without the diketone moiety in the curcumin molecule. Moreover, some structural modifications in keto-enol moiety have led to obtaining more information about different chemical and biological activities. Results obtained may be of interest for further research into combinations of curcumin and oleanolic acid derivatives.

Curcumin–Triterpene Type Hybrid as Effective Sonosensitizers for Sonodynamic Therapy in Oral Squamous Cell Carcinoma

“…General information on the conducted chemical experiments, as well as a description of the chemical structure of the synthesized compounds, can be found in our previous publication [ 35 , 38 ].…”

“…Curcumin pyrazole (5) was prepared by heterocyclization of a diketone system with hydrazine dihydrochloride (Scheme 2). In previous work [38], selected monoester hybrid-type derivatives based on curcumin or its heterocyclic analogs (pyrazole or isoxazole) and oleanolic acid with the succinic acid moiety were obtained. In this case, the synthesis of the hybrid derivative 7 was carried out by reacting the phenolic group of the curcumin pyrazole (5) with the free carboxyl group of the 4-carbon linker oleanoyl hydrogen succinate (6) in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) (Scheme 3).…”

“…In this case, the synthesis of the hybrid derivative 7 was carrie out by reacting the phenolic group of the curcumin pyrazole (5) with the free carboxy group of the 4-carbon linker oleanoyl hydrogen succinate (6) in the presence of dicyclo hexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) (Scheme 3). In previous work [38], selected monoester hybrid-type derivatives based on curcumin or its heterocyclic analogs (pyrazole or isoxazole) and oleanolic acid with the succinic acid moiety were obtained. In this case, the synthesis of the hybrid derivative 7 was carried out by reacting the phenolic group of the curcumin pyrazole (5) with the free carboxyl group of the 4-carbon linker oleanoyl hydrogen succinate (6) in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) (Scheme 3).…”

“…In this case, the synthesis of the hybrid derivative 7 was carried out by reacting the phenolic group of the curcumin pyrazole (5) with the free carboxyl group of the 4-carbon linker oleanoyl hydrogen succinate (6) in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) (Scheme 3). General information on the conducted chemical experiments, as well as a description of the chemical structure of the synthesized compounds, can be found in our previous publication [35,38].…”

“…Similarly, the cytotoxicity of oleanolic acid oxime (2) was lower than that of 2 combined with US. On the General information on the conducted chemical experiments, as well as a description of the chemical structure of the synthesized compounds, can be found in our previous publication [35,38].…”