Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

Samir T Gaballah

doi:10.3797/scipharm.1507-02

Abstract

The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a–i) and sulfoxide (5a–h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a–i) and sulfoxide (5a–h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

Highlights

The high mortality caused by cancer puts it as the number one cause of death worldwide
The purity of compounds 3a-i was checked by thin-layer chromatography (TLC) and their melting points were in good agreement with the literature
The synthesized compounds were tested against four different tumor cell lines

Summary

Introduction

The high mortality caused by cancer puts it as the number one cause of death worldwide. This represents a great impact on human health, society, and the global economy. A large number of potent chemotherapeutic anticancer agents has been successfully identified, clinical treatments still suffer from many toxic side effects of the drugs such as bone marrow suppression, gastrointestinal tract lesions, nausea, hair loss, drug resistance, and so on [2]. Benzimidazole derivatives are commonly used chemical scaffolds because they play an important role in medicinal chemistry. They have earned an essential place in the list of chemotherapeutic agents. The synthesis of benzimidazoles has received much attention due to their antitumor and antiproliferative activities [12,13,14]

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Results

Conclusion