Synthesis of new 1,3-thiazol derivatives of maleopimaric acid as anticancer, antibacterial and antifungal agents

Abstract

A series of new 1,3-thiazole derivatives of maleopimaric acid 6a–f, 7a–f were synthesized and evaluated for anticancer, antibacterial and antifungal activities. Evaluation of cytotoxic activity against human embryonic kidney 293 cells (HEK293), human neuroblastoma cell line (SH-SY5Y), hepatocellular carcinoma cell line (HepG2) and human T-cell lymphoblast-like line (Jurkat), showed that introduction of the aminothiazole fragment at position 6 of the diterpenoid molecule leads to decrease of cell viability. Substance 3 was found to be the most active against all tested cell lines, inhibiting cell viability with IC₅₀ values in the range of 2–24 μM. The structure–activity relationship of these compounds was studied and the results show that the compounds 6c and 7e exhibited in vitro antifungal activity against Candida albicans and also possessed antibacterial profile against Enterobacter aerogenes, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Proteus vulgaris.

Keywords:

• Maleopimaric acid
• α-bromoketones
• α-diazoketone
• thiourea
• Hantzsch reaction
• thiazoles
• cytotoxic activity
• antimicrobial activity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by State assignments № AAAA-A17-117011910025-6, № AAAA-A17-117011910027-0 and № AAAA-A16-116020350033-8. Experiments were carried out using the equipment of Collective Use Service Centers «Chemistry» and «Biomics».