Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity.

Juan Ma,Guo-Hua Gong

doi:10.3390/molecules27051537

Abstract

In this paper, a small series of novel quinoline sulfonamide derivatives was synthesized, and their structure of the target compounds were confirmed by 1H NMR and MS. The screening of the news target compounds’ in vitro cytotoxic activities against tumor cell lines by the MTT method was performed. Among them, compound D13 (N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC50: 1.34 μM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC50: 6.74 μM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further modification.

Highlights

The mortality rate and the incidence of cancer are increasing year by year
The biggest difference between cancer and normal cells is that the proliferation of cancer cells is abnormally frequent and often uncontrolled, which makes tumor cell growth heavily dependent on the dynamic instability of tubulins/microtubules involved in polymerization and depolymerization [7,8]
The target compounds D1–D16 were obtained by the nucleophilic substitution reaction between A and C [24]

Summary

Introduction

The mortality rate and the incidence of cancer are increasing year by year. The number of patients who die of malignant tumors worldwide has risen to the second place among various causes of death, which seriously threatens human health [1,2]. The biggest difference between cancer and normal cells is that the proliferation of cancer cells is abnormally frequent and often uncontrolled, which makes tumor cell growth heavily dependent on the dynamic instability of tubulins/microtubules involved in polymerization and depolymerization [7,8]. The endothelial cells involved in tumor angiogenesis are immature and need a skeletal network composed of microtubules to maintain their morphology [9,10]. By inhibiting the polymerization of tubulin into microtubules during tumor cell division, or inhibiting the depolymerization of microtubules into microtubules, mitosis will be unable to proceed or stop, and induce the occurrence of apoptosis, so as to achieve the purpose of inhibiting the growth of tumor cells [11]. Since microtubules play a very critical role in the growth and development of tumor cells, they have become an ideal target for anti-tumor drug research [12]

Methods

Results

Conclusion