Related Experiment Video
Updated: Jun 9, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and Cytotoxicity of Complex Betulinic Acid Amides
Martina Wimmerová1, Pavlína Kyjaková2, David Šaman2
1Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technická 5, 16028 Prague 6, Czech Republic.
Abstract:
The main objective of this investigation was focused on the structure modification of betulinic acid to design novel cytotoxic compounds. The cytotoxicity of the amides of betulinic acid with several diamines was compared with that of the compounds bearing an additional amide bond formed by means of 4-methoxybenzoic acid. It was prepared by a green biotechnological approach from trans-anethole isolated from anise (Pimpinella anisum L.) seeds. Cisplatin and doxorubicin, the pharmacologically used anticancer agents, were used as the positive references. One of the target compounds (9) showed cytotoxicity in HeLa (IC50 = 5.4 ± 0.8 μM; SI > 9.3) and MCF7 (IC50 = 7.0 ± 1.1 μM; SI > 7.2) cancer cell lines while being nontoxic in normal human foreskin fibroblasts (IC50 > 50 μM), and it showed a better cytotoxicity profile than structurally related compounds 8 and 10. The aromatic substituent and the C(3)-OAc group in 9 were also advantageous for the cytotoxicity profile of 9 in comparison with its intermediate compound 8. Several intermediates and target compounds showed a better cytotoxicity profile than cisplatin.
Related Concept Videos
Preparation of Amides
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
Physical Properties of Amines
Antifungal Agents
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Amides to Carboxylic Acids: Hydrolysis
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Basicity of Heterocyclic Aromatic Amines

