Synthesis and cytotoxic evaluation of a series of 2-amino-naphthoquinones against human cancer cells.

Thiago De Moraes,George Ximenes,Valdemiro Silva,Celso Camara,Igor Bomfim,Bruno Soares,Maria Filha,Claudia Pessoa,Tania Silva

doi:10.3390/molecules190913188

Abstract

The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma), MDAMB-435 (breast), HCT-8 (colon), HCT-116 (colon), HL-60 (leukemia), OVCAR-8 (ovarian), NCI-H358M (bronchoalveolar lung carcinoma) and PC3-M (prostate) cancer cells and also against PBMC (peripheral blood mononuclear cells). The results demonstrated that all the synthetic aminonaphthoquinones had relevant cytotoxic activity against all human cancer lines used in this experiment. Five of the compounds showed high cytotoxicity and selectivity against all cancer cell lines tested (IC50 = 0.49 to 3.89 µg·mL−1). The title compounds were less toxic to PBMC, since IC50 was 1.5 to eighteen times higher (IC50 = 5.51 to 17.61 µg·mL−1) than values shown by tumour cell lines. The mechanism of cell growth inhibition and structure–activity relationships remains as a target for future investigations.

Highlights

518,510 new cases of cancer were estimated for Brazil between 2012 and 2013, including cases of non-melanoma skin cancer, which is the most common type for both men and women (134,000 new cases), followed by prostate (60,000), female breast (53,000), colon and rectum (30,000), lung (27,000), stomach (20,000) and cervix (18,000) [1].Quinones and their derivatives are substances naturally obtained or synthesized in the laboratory [2]with multiple biological functions in the metabolic cycles of various organisms [3,4]
The title compounds were obtained in an one-pot Michael nucleophilic 1,4-addition procedure (Scheme 1) from commercially available 1,4-naphthoquinone (1) and suitable α- and other amino acids or esters thereof [13,14]
Our findings have demonstrated the cytotoxic potential against human cancer lines of a series of synthetic aminoacids conjugated with a naphthoquinone nucleus

Summary

Introduction

518,510 new cases of cancer were estimated for Brazil between 2012 and 2013, including cases of non-melanoma skin cancer, which is the most common type for both men and women (134,000 new cases), followed by prostate (60,000), female breast (53,000), colon and rectum (30,000), lung (27,000), stomach (20,000) and cervix (18,000) [1].Quinones and their derivatives are substances naturally obtained or synthesized in the laboratory [2]with multiple biological functions in the metabolic cycles of various organisms [3,4]. 518,510 new cases of cancer were estimated for Brazil between 2012 and 2013, including cases of non-melanoma skin cancer, which is the most common type for both men and women (134,000 new cases), followed by prostate (60,000), female breast (53,000), colon and rectum (30,000), lung (27,000), stomach (20,000) and cervix (18,000) [1] Quinones and their derivatives are substances naturally obtained or synthesized in the laboratory [2]. The major natural sources are higher plants, arthropods, fungi, lichens, bacteria, algae and viruses They are classified in accordance with the aromatic system present in their structures; naphthoquinones are related to the naphthalenic ring. Lee and some co-workers [9] demonstrated that β-lapachone, present in

Methods

Results

Conclusion