Microwave-Assisted Synthesis of New Selenazole Derivatives with Antiproliferative Activity

Adriana Grozav Ignat,Victor Kuete,Luminita Silaghi-Dumitrescu,Luiza Gaina,Valentin Zaharia,Thomas Efferth

doi:10.3390/molecules18044679

Abstract

New aryl-hydrazinyl-1,3-selenazole and aroyl-hydrazonyl-1,3-selenazoles were synthesized via Hantzsch type condensation reactions of selenosemicarbazides with α-halogenocarbonyl derivatives, under classical versus microwave heating conditions. Excellent yields and shorter reaction times were obtained under irradiation conditions. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR, 1H-NMR), MS and elemental analysis. Selenazole derivatives were screened for their anti-proliferative effects against two leukemia cell lines (CCRF-CEM and HL60) and three carcinoma cell lines (MDA-MB231, HCT116 and U87MG).

Highlights

Selenium is an essential element for organisms, but its beneficial effects on human health are strongly dependent on concentration and on chemical form
The new arylidenehydrazinoselenazoles 3a–e and aroylhydrazinoselenazoles 5a–c were prepared via Hantzsch condensation reactions of a selenosemicarbazone or benzoylselenosemicarbazide with a series of α-halocarbonyl derivatives
The molecular ion, accompanied by the isotopic peaks confirms the molecular weight of the selenazole derivatives [i.e., in the EIMS spectra for compound 5b, all the isotopic peaks for selenium are present, 351(78Se), 350(77Se), 349(76Se), 353 (80Se), 355 (82Se)]

Summary

Introduction

Selenium is an essential element for organisms, but its beneficial effects on human health are strongly dependent on concentration and on chemical form. The genotoxic and cytotoxic effects of organoselonium derivatives in human leukocyte cells and V79 Chinese lung fibroblast cells can be associated to the pro-oxidant activity exhibited by selenium compounds when used in relatively high concentrations [19,20]. The lipophilicity and anticancer activity of a number of selenazole derivatives were investigated to better understand the correlation between drug delivery and permeation across a biological membrane [22,23,24]. Continuing our effort in the synthesis and in the characterization of the biological activity of new selenazole derivatives, we describe here the results of our investigations regarding the anti-proliferative effects against two leukemia cell lines and three carcinoma cell lines. The most important advantages induced by microwaves in organic synthesis consist in reduced reaction times, high yields and enhanced reaction rates [28]

Results and Discussion

General

Cytotoxicity Assay

Conclusions