Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

Carolina Ribeiro E Silva,Caridad Noda Perez,Daniela De Melo E Silva,Flávio Fernandes Veloso Borges,Lee Chen-Chen,Aline Bernardes,Praveen Rishi

doi:10.1371/journal.pone.0137063

Carolina Ribeiro E Silva, Caridad Noda Perez + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0137063

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Journal: PloS one	Publication Date: Sep 3, 2015
Citations: 18	License type: CC BY 4.0

Affiliation: Universidade Federal de Goiás

Abstract

Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

Highlights

Chalcones are natural compounds of widespread occurrence in plants and considered precursors of flavonoids
The data obtained for the positive and negative control groups indicated that the strains were in agreement with the guidance established by Maron and Ames [16] and Mortelmans and Zeiger [11]
Based on the dose-response relation of a large number of doses tested, we can infer that chalcone N-{4[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) presented a moderate profile of a mutagenic compound

Summary

Introduction

Chalcones are natural compounds of widespread occurrence in plants and considered precursors of flavonoids They can be synthesized by Claisen-Schmidt condensation between benzaldehydes and acetophenones using either basic or acidic catalysis [1,2]. These compounds have been reported to exhibit a wide range of pharmaceutical effects, including antioncogenetic, anti-inflammatory, anti-ulcerative, antimalarial, antiviral, antifungal, and antibacterial activities [3]. Some of their derivatives have proven to be antimutagenic [4]. Considering the importance of chalcones and sulfonamides for further therapeutic development, it is relevant to evaluate the genotoxic and antigenotoxic activities of these compounds

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