An In Vitro Antimicrobial, Anticancer and Antioxidant Activity of N–[(2–Arylmethylthio)phenylsulfonyl]cinnamamide Derivatives

Abstract

Cinnamic acid is a plant metabolite with antimicrobial, anticancer, and antioxidant properties. Its synthetic derivatives are often more effective in vitro than parent compounds due to stronger biological activities. In our study, we synthesized ten new N–(4–chloro–2–mercapto–5–methylphenylsulfonyl)cinnamamide derivatives, containing two pharmacophore groups: cinnamic acid moiety and benzenesulfonamide. The antimicrobial activity of the obtained compounds was estimated using different types of Gram-positive and Gram-negative bacteria, fungus species of Candida albicans, as well as clinical strains. The compounds were evaluated on biofilm formation and biofilm formed by Staphylococcus clinical strains (methicillin–resistance S. aureus MRSA and methicillin–resistance coagulase–negative Staphylococcus MRCNS). Furthermore, blood bacteriostatic activity test was performed using S. aureus and S. epidermidis. In cytotoxic study, we performed in vitro hemolysis assay on domestic sheep peripheral blood and MTT [3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide] assay on human cervical HeLa, ovarian SKOV-3, and breast MCF-7 cancer cell lines. We also estimated antioxidant activity of ten compounds with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′–azino–bis(3–ethylbenzthiazoline–6–sulfonic acid) (ABTS) assays. Our results showed a significant antimicrobial activity of the compounds. All of them were active on Staphylococcus and Enterococcus species (MIC was 1–4 µg/mL). The compounds 16d and 16e were the most active on staphylococci clinical strains and efficiently inhibited the biofilm formation and biofilm already formed by the clinical staphylococci. Moreover, the hemolytic properties of the tested compounds occurred in higher quantities (>32.5 µg/mL) than the concentrations that inhibited both the growth of bacteria in the blood and the formation and growth of biofilm. The results of MTT assay showed that compounds 16c, 16d, 17a, and 17d demonstrated the best activity on the cancer cells (the IC50 values were below 10 µg/mL). Compound 16f was the least active on the cancer cells (IC50 was > 60 µg/mL). Antiradical tests revealed that compounds 16f and 17d had the strongest antioxidant properties within the tested group (IC50 was 310.50 ± 0.73 and 574.41 ± 1.34 µg/mL in DPPH, respectively, and 597.53 ± 1.3 and 419.18 ± 2.72 µg/mL in ABTS assay, respectively). Our study showed that the obtained cinnamamide derivatives can be used as potential antimicrobial therapeutic agents.

New Chalcone Derivatives Containing 2,4-Dichlorobenzenesulfonamide Moiety with Anticancer and Antioxidant Properties

“…To estimate the cytotoxic effect of the five compounds ( 4 – 8 ), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used [ 38 ]. Oxaliplatin was used as a positive control in this test.…”

“…The DPPH radical scavenging assay of samples (ligands or complexes) was performed with ascorbic acid as a standard [ 38 , 69 ]. Different concentrations of chalcone derivatives, dissolved in DMSO, were mixed with the same amount of 0.06 mM DPPH methanolic solution and incubated at room temperature in the dark for 30 min.…”

“…The current study is a continuation of our team’s research on innovative hybrid compounds [ 37 , 38 ]. We designed and synthesized ( E )-2,4-dichloro- N -(4-cinnamoylphenyl)-5-methylbenzenesulfonamide derivatives incorporating the following two pharmacophore groups: 2,4-dichlorobenzenesulfonamide (A) and chalcone (B), as illustrated in Figure 1 .…”

An investigation of the biological applications of sulphonated succinimides: in vivo toxicity to zebrafish larvae as well as antioxidant and antimicrobial potential

“…In recent years, many investigations have recorded the antioxidant properties of succinimide and sulphonyl moieties. A few examples are as follows: ruthenium complexes with succinimide ligands act against HL-60 leukemic cells and PBMCs, 26 the antioxidant potential of aldehydic-pyrrolidinedione against free radicals (ABTS, DPPH, and H 2 O 2 ), 1 the antioxidant property of ketoesters derivatives allow them to be used as supplements for the treatment of Alzheimer's disease, 12 sulfonyl ester-based heterocyclic Schiff bases against β-carotene linoleic acid and CUPRAC assays, 27 and bis(aroyl/arylsulfonyl ethene sulfonyl methyl azolyl)pyridine 28 and N -[(2-arylmethylthio)phenylsulfonyl] cinnamamide 29 against free radicals. Antibacterial studies of succinimide and sulphonyl moieties have also been reported.…”

A formal vinylic substitution reaction for the synthesis of α,β-unsaturated enol esters and their anticancer potential

“…The ‘cinnamoyl group’ functions as the major pharmacophore unit of numerous designed anticancer agents including esters, amides, sulfonamides and chalcones. 1…”