Thiazolidin-4-ones is an important heterocyclic ring system of a pharmacophore and a privileged scaffold in medicinal chemistry. This review is focused on the latest scientific reports regarding biological activities of thiazolidin-4-ones published in 2020 and 2021. The review covers recent information about antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, antidiabetic, antiparasitic, antimicrobial, antitubercular and antiviral properties of thiazolidin-4-ones. Additionally, the influence of different substituents in molecules on their biological activity was discussed in this paper. Thus, this study may help to optimize the structure of thiazolidin-4-one derivatives as more efficient drug agents. Presented information may be used as a practical hint for rational design of new small molecules with biological activity, especially among thiazolidin-4-ones.

In our present research, we synthesised new thiazolidine-2,4-diones (12–28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC₅₀ values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC₅₀ values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment. Graphical Abstract

The two series of thiosemicarbazone derivatives with thiazolidine-2,4-dione (TZD) core were designed and synthesized. The antimycobacterial activity of the target compounds was tested against Mycobacterium tuberculosis H37Ra by broth microdilution method with resazurin as an indicator of the metabolic activity of mycobacteria. Conducted studies revealed antimycobacterial activity in the concentration range of 0.031-64 µg/ml for 31 synthesized derivatives with TZD core. The highest antimycobacterial activity (MIC = 0.031-0.125 µg/ml) was demonstrated for the new group of compounds: TZD-based hybrids with 4-unsubstituted thiosemicarbazone substituent. Furthermore, all the tested compounds within this group were characterized by low cytotoxicity. Among tested compounds, two compounds are the most promising potential antimycobacterial agents since they not only show very low MIC values, but also non-toxicity against Vero cells at tested concentration range. High effectiveness and safety of these synthesized compounds makes them promising candidates as antimycobacterial agents.

A series of new (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid derivatives with thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin moiety (28-65) were synthesized by the reaction of (2,4-dioxothiazolidin-5-yl/ylidene)acetic acid chlorides with 5-(hydroxybenzylidene) thiazolidine-2,4-dione, rhodanine and 2-thiohydantoin derivatives. Obtained compounds (28-65) were tested on reference strains of Gram-positive bacteria and ones of the Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth microdilution method. These derivatives showed antibacterial activity generally against Gram-positive bacterial strains. Most active compounds possess MIC = 3.91 mg/L. Our results suggest that presence of electron-withdrawing substituent at phenyl ring is favorable while geometry of molecule does not play important role in antibacterial response. It was confirmed the lack of direct influence of substitution pattern at phenyl ring on antibacterial activity of closely related compounds of series 1-3. The antibacterial activity of some compounds was similar or higher than the activity of commonly used reference drugs such as oxacillin and cefuroxime.

Series of new thiazolidine-2,4-dione-based chlorophenylthiosemicarbazone hybrids (17–40) were synthesized by the reaction of condensation chlorophenylthiosemicarbazides with formylphenyl 2-(2,4-dioxothiazolidin-5-yl/ylidene)acetates. New compounds were tested on reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity of target compounds was determined by broth dilution method. Most active compounds possess minimum inhibitory concentration (MIC) = 3.91 mg/L. These compounds were non-toxic at concentrations close to their antibacterial effect. The antibacterial activity of some compounds was similar to or higher than the activity of used reference drugs such as oxacillin and cefuroxime. The structure–activity relationships (SARs) analysis collectively suggests that at least two different molecular mechanisms of their antibacterial activity should be expected.