Synthesis and Biological Evaluation of Novel Dehydroabietic Acid Derivatives Conjugated with Acyl-Thiourea Peptide Moiety as Antitumor Agents

TL;DR

Researchers designed and tested new antitumor compounds based on dehydroabietic acid, finding one that effectively kills cancer cells while being less harmful to normal cells.

Contribution

A new class of antitumor agents based on dehydroabietic acid conjugated with acyl-thiourea peptide moieties was synthesized and evaluated.

Findings

Compound 9n showed strong antitumor activity against HeLa cells with an IC50 of 6.58 μM.

Compound 9n induced apoptosis in HeLa cells through a mitochondrial pathway.

Compound 9n arrested HeLa cells in the S phase of the cell cycle.

Abstract

A series of dehydroabietic acid (DHAA) acyl-thiourea derivatives were designed and synthesized as potent antitumor agents. The in vitro pharmacological screening results revealed that the target compounds exhibited potent cytotoxicity against HeLa, SK-OV-3 and MGC-803 tumor cell lines, while they showed lower cytotoxicity against HL-7702 normal human river cells. Compound 9n (IC50 = 6.58 ± 1.11 μM) exhibited the best antitumor activity against the HeLa cell line and even displayed more potent inhibitory activity than commercial antitumor drug 5-FU (IC50 = 36.58 ± 1.55 μM). The mechanism of representative compound 9n was then studied by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay and flow cytometry, which illustrated that this compound could induce apoptosis in HeLa cells. Cell cycle analysis indicated that compound 9n mainly arrested HeLa cells in the S phase stage. Further investigation demonstrated that compound 9n induced apoptosis of HeLa cells through a mitochondrial pathway.

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