Semisynthetic and SAR Studies of Amide Derivatives of Neocrotocembraneic Acid as Potential Antitumor Agents.

Hai Shang,Zhong-Mei Zou,Ling-Yu Li,Wei-Hua Cheng,Hong-Wu Zhang,Jun Luo

doi:10.3390/molecules21111581

Abstract

A series of novel amide derivatives of cembranoid neocrotocembraneic acid were designed and synthesized. The antiproliferative activities of these derivatives were evaluated against three human tumor cell lines (the human cervical cancer cell line HeLa, chronic myeloid leukemia cell line K562 and leukemia multidrug-resistant cell line K562/A02). Some of the synthesized compounds exhibited moderate to good activity against all three cancer cell lines. Particularly, compound 8a exhibited more potent antiproliferative activity than the reference drug etoposide against drug-resistant cell line K562/A02, indicating that it possessed a great potential for further development as a multidrug resistance modulator by structural modification.

Highlights

Cembranoids are natural diterpenes possessing 14-membered macrocyclic rings substituted by an isopropyl residue at C-1 and by three symmetrically disposed methyl groups at positionsC-4, C-8, and C-12 [1]
The antitumor activity of these compounds was evaluated against the human cervical cancer cell line HeLa and neocrotocembraneic acid showed modest cytotoxic activity (IC50 = 45.4 μM)
All synthesized compounds were evaluated for their antitumor activity against three cancer cell

Summary

Introduction

Cembranoids are natural diterpenes possessing 14-membered macrocyclic rings substituted by an isopropyl residue at C-1 and by three symmetrically disposed methyl groups at positionsC-4, C-8, and C-12 [1]. Cembranoids are natural diterpenes possessing 14-membered macrocyclic rings substituted by an isopropyl residue at C-1 and by three symmetrically disposed methyl groups at positions. More than 300 natural cembranoid derivatives were isolated and their structural diversity is mainly reflected in the different degrees of oxidation of the macrocyclic framework [4]. We have reported studies on the chemical composition of the leaves of C. laevigatus Vahl. The antitumor activity of these compounds was evaluated against the human cervical cancer cell line HeLa and neocrotocembraneic acid showed modest cytotoxic activity (IC50 = 45.4 μM). This natural product has a high content in C. laevigatus Vahl.

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Conclusion