Synthesis and cytotoxic effect of a few N-heteroaryl enamino amides and dihydropyrimidinethiones on AGS and MCF-7 human cancer cell lines

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Date: March-April 2020
From: Research in Pharmaceutical Sciences(Vol. 15, Issue 2)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 3,767 words
Lexile Measure: 1410L

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Byline: Sajjad. Tavangar, Shahab. Bohlooli, Nima. Razzaghi-Asl

Background and purpose: Cancer prevalence has increased in the last century posing psychological, social, and economic consequences. Chemotherapy uses chemical molecules to control cancer. New studies have shown that dihydropyrimidinethione (DHPMT) derivatives have the potential of being developed into anticancer agents. Experimental approach: New derivatives of DHPMTs and a few acyclic bioisosters were synthesized via Biginelli reaction and assessed for their toxicity against gastric (AGS) and breast cancer (MCF-7) cell lines through MTT method. Findings / Results: Chemical structures of all synthesized N-heteroaryl enamino amides and DHPMTs were confirmed by spectroscopic methods. Result of biological assessment exhibited that none of the tested agents was more cytotoxic than cis-platin against AGS and MCF-7 cell lines and compound 2b was the most cytotoxic agent against AGS (IC[sub]50 41.10 ?) and MCF-7 (IC[sub]50 75.69 ?). Cytotoxic data were mostly correlated with the number of H-bond donors within gastric and breast cancer cells. Conclusion and implications: It was realized that DHPMTs were able to inhibit the growth of cancer cells much better than acyclic enamino amides and moreover;N-(4-methylbenzothiazol-2-yl) DHPMT derivative (2b) supposed possible interaction with a poor electron site of target due to the lipophilic nature of benzothiazole ring and also less electron rich nature than isoxazole. Similar scenario was observed with acyclic enamino amides in which incorporation of sulfur and nitrogen containing heterocycles doubled the cytotoxic effects. Results of the present contribution might assist in extending the scope of DHPMTs as privileged medicinal scaffolds.

Introduction

Cancer is the largest family of non- infectious diseases. There is a common point in all types of this disease, which is the high and non-controllable multiplicationof certain cells in the patient's body.

The causes of cancer are very diverse and widespread. It has been revealed that 90-95% of cancers are the result of genetic mutations caused by environmental or lifestyle factors and the remaining 5 to 10 percent are due to heredity [1].

Environmental factors include lifestyle, economics, behavior, and the living environment.

In a smaller perspective, these factors include chemicals and outside factors (2530%), obesity (30-35%), infections (15-20%), and radiation (15-20%) [2].

According to the World Health Organization (WHO) on September 12, 2018, there were 18.1 million new cases of cancer and 9.6 million deaths due to cancer worldwide this year. Starting from September 12, 2013 to September 12, 2018, there were 43.8 million deaths recorded due to cancer worldwide. These statistics indicate the high importance of cancer in death rates [3]. In the light of the high prevalence of the disease, its treatment or control is a key priority [4].

Heterocycles are privileged structures in biochemical processes since their chemical structure is present in important biological compounds and living cells. Among the heterocyclic compounds existing in nature, nitrogen-containing ones are more important than others due to their distribution in nucleic acids, amino acids, and also their interference in the physiological processes of plants and animals. Recent studies have shown that N- heteroaryl derivatives can be effective in control...

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Gale Document Number: GALE|A624238018