Utility of 3-Acetyl-6-bromo-2H-chromen-2-one for the Synthesis of New Heterocycles as Potential Antiproliferative Agents.

Sobhi Gomha,Yasser Zaki,Abdou Abdelhamid

doi:10.3390/molecules201219803

Sobhi Gomha, Yasser Zaki + Show 1 more

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https://doi.org/10.3390/molecules201219803

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Abstract

Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl chlorides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Moreover, selected newly synthesized products were evaluated for their antitumor activity against a liver carcinoma cancer cell line (HEPG2-1). The results revealed that pyrazolo[1,5-a]pyrimidine 7c, thiazole 23g and 1,3,4-thiadiazole 18a (IC50 = 2.70 ± 0.28, 3.50 ± 0.23 and 4.90 ± 0.69 µM, respectively) have promising antitumor activity against liver carcinoma (HEPG2-1) while most of the tested compounds showed moderate activity.

Highlights

The synthesis of coumarins and their derivatives has attracted considerable attention from organic and medicinal chemists for many years as a large number of natural and synthetic products contain this heterocyclic nucleus
In continuation of our research program on the synthesis of novel heterocyclic compounds exhibiting antitumor activities [22,23,24,25,26], we attempted to design pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]-pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyridazine, thiazoles, and thiadiazoles linked to position 3 of coumarin as a novel 3-heteroarylcoumarins, which have not been reported hitherto, to evaluate their in vitro antitumor activity against a liver carcinoma cell line (HEPG2-1)
The results revealed that the descending order of activity of the newly synthesized compounds was as follows: 7c > 23g > 18a > 12a > 23c > 8a > 7b > 7e > 18f > 7a > 7d > 23d > 12b > 18c > 13a

Summary

Introduction

The synthesis of coumarins and their derivatives has attracted considerable attention from organic and medicinal chemists for many years as a large number of natural and synthetic products contain this heterocyclic nucleus. The antitumor activity of coumarin compounds has received considerable attention among researchers because of their cytotoxic activity against numerous types of cancers, including malignant melanoma, leukemia, renal cell carcinoma, prostate and breast cancer cell progression [8,9,10]. The antitumor activities of coumarin were tested in several human tumor cell lines by Steffen et al [13]. In continuation of our research program on the synthesis of novel heterocyclic compounds exhibiting antitumor activities [22,23,24,25,26], we attempted to design pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]-pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyridazine, thiazoles, and thiadiazoles linked to position 3 of coumarin as a novel 3-heteroarylcoumarins, which have not been reported hitherto, to evaluate their in vitro antitumor activity against a liver carcinoma cell line (HEPG2-1)

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