Synthesis and Evaluation of New Podophyllotoxin Derivatives with in Vitro Anticancer Activity.

Wei-Hua Cheng,Cong Niu,Li-Ming Zhang,Hai Shang,Zhong-Mei Zou,Zhong-Heng Zhang,Hong Chen

doi:10.3390/molecules200712266

Abstract

A series of novel podophyllotoxin derivatives were designed and synthesized. The cytotoxic activities of these compounds were tested against three tumor cell lines (HeLa, K562, and K562/A02). Most of the derivatives (IC50 = 1–20 μM) were found to have stronger cell growth inhibitory activity than positive control etoposide. Among them, 4β-N-[(E)-(5-((4-(4-nitrophenyl)-piperazin-1-yl)methyl)furan-2-yl)prop-2-en-1-amine]-4-desoxy-podophyllotoxin (9l) demonstrated significant inhibitory activity against HeLa, K562, and K562/A02 cell lines with IC50 values of 7.93, 6.42, 6.89 μM, respectively.

Highlights

Cancer is a major public health problem in the world
The synthesis of compounds 4a–i is outlined in Scheme 1
Cytotoxicities of all target derivatives were evaluated against three human cancer cell lines by the MTT assay

Summary

Introduction

Cancer is a major public health problem in the world. In 2008, 7.6 million people died of cancer (around 13% of all deaths), and this number is projected to increase with an estimated 13.1 million in 2030 [1].Podophyllotoxin (PPT, a), the most abundant naturally occurring cyclolignan isolated mainly fromPodophyllum peltatum and P. hexandrum, has important antineoplastic and antiviral properties [2].its antimitotic activity is proved to be of the greatest interest to researchers [3]. Cancer is a major public health problem in the world. In 2008, 7.6 million people died of cancer (around 13% of all deaths), and this number is projected to increase with an estimated 13.1 million in 2030 [1]. Podophyllotoxin (PPT, a), the most abundant naturally occurring cyclolignan isolated mainly from. Podophyllum peltatum and P. hexandrum, has important antineoplastic and antiviral properties [2]. Its antimitotic activity is proved to be of the greatest interest to researchers [3]. Because of its toxic side effects, extensive structural modifications were performed since the 1950s. Podophyllotoxin derivatives possess antitumor activity, such as etoposide (VP-16, b) and teniposide (VM-26, c) (Figure 1)

Methods

Results

Conclusion