Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes.

Aleksandra Włoch,Barbara Bażanów,Fouad Bahri,Dominika Stygar,Witold Gładkowski,Elżbieta Chełmecka,Piotr Kuropka,Hanna Pruchnik

doi:10.3390/biom10121594

Abstract

The aim of this work was the examination of biological activity of three selected racemic cis-β-aryl-δ-iodo-γ-lactones. Tested iodolactones differed in the structure of the aromatic fragment of molecule, bearing isopropyl (1), methyl (2), or no substituent (3) on the para position of the benzene ring. A broad spectrum of biological activity as antimicrobial, antiviral, antitumor, cytotoxic, antioxidant, and hemolytic activity was examined. All iodolactones showed bactericidal activity against Proteus mirabilis, and lactones 1,2 were active against Bacillus cereus. The highest cytotoxic activity towards HeLa and MCF7 cancer cell lines and NHDF normal cell line was found for lactone 1. All assessed lactones significantly disrupted antioxidative/oxidative balance of the NHDF, and the most harmful effect was determined by lactone 1. Contrary to lactone 1, lactones 2 and 3 did not induce the hemolysis of erythrocytes after 48 h of incubation. The differences in activity of iodolactones 1–3 in biological tests may be explained by their different impact on physicochemical properties of membrane as the packing order in the hydrophilic area and fluidity of hydrocarbon chains. This was dependent on the presence and type of alkyl substituent. The highest effect on the membrane organization was observed for lactone 1 due to the presence of bulky isopropyl group on the benzene ring.

Highlights

Cancer is one of the most serious causes of human death worldwide
The results indicated that lactones 1–3 did not show any antifungal activity which was in some contrast to our previous investigations in which lactones 1 and 2 inhibited up to 50% of the mycelium growth of four Fusarium strains (F.culmorum, F.avenaceum, F.oxysporum, and F.solani) [15]
The growth of B.cereus was inhibited to a lesser extent only by lactones 1 and 2, with 9 mm ± 0.58 and 7 mm ± 0.01 zones, respectively, which was lower than that determined for doxocycline (19 mm ± 1.41)

Summary

Introduction

Cancer is one of the most serious causes of human death worldwide. Despite the introduction of many new anticancer drugs on the pharmaceutical market, mortality is very high, reaching about 9.6 million deaths in 2018 according to the World Health Organization [1]. One of the factors leading to cancer may be bacterial, viral, and fungal infections. Infection of the urinary tract with Staphylococcus aureus, Klebsiella spp., Proteus mirabilis, and Escherichia coli has been found to cause bladder cancer. While the exact mechanism by which bacterial infections induce cancer is not fully understood, it is believed that it may be due to the release of free radicals which further damage DNA and regulatory proteins [4,5,6]

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