Design, Synthesis and Cytotoxic Evaluation of Novel Heterocyclic Thioglycosides

Elgemeie Gh

doi:10.4172/2161-0444.1000234

Abstract

A novel series of 2-thioxoimidazolidin-4-one and Benzothiazole thioglycosides were synthesized via one-pot reaction of the 2-thioxoimidazolidin-4-one and Benzothiazole thiolate salts, respectively with 2,3,4,6-tetra-O-acetyl- α-D-gluco- and galactopyranosyl bromides. The cytotoxic activity of compound 7, 8a, 8b, 10a, 10b, 15a and 15b were evaluated against MCF-7 cell lines (Breast carcinoma cell lines) showing high to moderate anti-tumor activities moreover molecular modeling of these compounds revealed that they have high binding affinity through hydrophobichydrophobic interaction and moderate selectivity through the hydrogen bond interaction with the atypical nucleotide binding pocket in the amino terminus of HSP90.

Highlights

According to the world health organization (WHO), cancer is an important health problem that claims the level of more than 7 million people world wide on an annual basis [1,2]
A series of triazole-containing novobiocin analogues has been designed, the anti-proliferative effects of these compounds were evaluated against breast cancer cell lines, and the manifested activities were similar to their amide-containing counterparts [48]
In view of these observations and with the aim of identifying new anticancer agents with improved pharmacokinetic and safety profile, it was considered valuable to synthesize some new non classical nucleoside derivatives incorporating heterocyclic other than coumarin and/or functionalized aryl derivatives carrying carbohydrate residues through S-glycosidic bond as anti-cancer agents especially against breast carcinoma which could be capable of inhibiting Heat shock protein 90 (HSP90) function by potential interaction towards the binding pocket in the amino terminus of HSP90

Summary

Introduction

According to the world health organization (WHO), cancer is an important health problem that claims the level of more than 7 million people world wide on an annual basis [1,2]. A series of triazole-containing novobiocin analogues has been designed, the anti-proliferative effects of these compounds were evaluated against breast cancer cell lines, and the manifested activities were similar to their amide-containing counterparts [48] In view of these observations and with the aim of identifying new anticancer agents with improved pharmacokinetic and safety profile, it was considered valuable to synthesize some new non classical nucleoside derivatives incorporating heterocyclic other than coumarin and/or functionalized aryl derivatives carrying carbohydrate residues through S-glycosidic bond as anti-cancer agents especially against breast carcinoma which could be capable of inhibiting HSP90 function by potential interaction towards the binding pocket in the amino terminus of HSP90. The spectrum showed the 5 aromatic protons as a multiplet at δ 7.00-7.57 ppm of the aglycon part In this investigation, we introduce a novel synthesis of benzothiazole thioglycosides derivatives as a new class of glycosides.

Materials and methods

Conclusion