Abstract
Heterocycles are commonly known for their unique features, e.g., antibacterial or anticancer properties. Although many synthetic heterocycles, such as 4-thiazolidinone (4-TZD), have been synthesized, their potential applications have not yet been fully investigated. However, many researchers have reported relevant results that can be a basis for the search for new potential drugs. Therefore, the aim of this study was to evaluate the cytotoxic, cytostatic, and antibacterial effects of certain 4-thiazolidinone-based derivatives, Les-3166, Les-5935, Les-6009, and Les-6166, on human fibroblasts (BJ), neuroblastoma (SH-SY5Y), epithelial lung carcinoma (A549), and colorectal adenocarcinoma (CACO-2) cell lines in vitro. All tested compounds applied in a concentration range from 10 to 100 µM were able to decrease metabolic activity in the BJ, A549, and SH-SY5Y cell lines. However, the action of Les-3166 was mainly based on the ROS-independent pathway, similarly to Les-6009. In turn, Les-5935 and Les-6166 were able to promote ROS production in BJ, A549, and SH-SY5Y cells, compared to the control. Les-3166, Les-6009, and Les-6166 significantly increased the caspase-3 activity, especially at the concentrations of 50 µM and 100 µM. However, Les-5935 did not induce apoptosis. Only Les-5935 showed a minor cytostatic effect on SH-SY5Y cells. Additionally, the antibacterial properties of the tested compounds against P. aeruginosa bacterial biofilm can be ranked as follows: Les-3166 > Les-5935 > Les-6009. Les-6166 did not show any anti-biofilm activity. In summary, the study showed that Les-5935, Les-6009, and Les-6166 were characterized by anticancer properties, especially in the human lung cancer cell. In cases of BJ, SH-SY5Y, and CACO-2 cells the anticancer usage of such compounds is limited due to effect visible only at 50 and 100 µM.
Highlights
Small molecules based on different heterocyclic building blocks have been widely used in medicine, food industry, and biology [1]
Our results showed that none of the tested compounds possessed cytostatic effects, as indicated by the unaffected subpopulations at the G0/G1, S, or G2/M phases of the cell cycle, compared to the control
Our results have demonstrated that Les-3166 possesses high antibacterial properties, as it caused a decrease in biofilm biomass at the concentration range from 1 nM to 100 μM
Summary
Small molecules based on different heterocyclic building blocks have been widely used in medicine, food industry, and biology [1]. Due to the wide diversity of the structures of heterocycles, their physical and chemical properties differ substantially [2]. These properties do not fully illustrate/predict their biological effects in the cell; it is necessary to evaluate different heterocycle subtypes and consider their impact on biological systems. Heterocyclic compounds occur in the environment as part of plant secondary metabolites [3,4] and show various effects, including in vitro cytotoxicity towards some cancer cell lines [5]. Heterocycles are still of special interest in medicinal chemistry and the development of new drug-like molecules [1,6,7,8]
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