4-oxothiazolidine and Neoplasms

Cancer can be considered as a genetic as well as a metabolic disorder. The current cancer treatment scenario looks like aggravating tumor cell metabolism, causing the disease to progress even with greater intensity. The cancer therapy is restricted to the limitations of poor patient compliance due to toxicities to normal tissues and multi-drug resistance development. There is an emerging need for cancer therapy to be more focused towards better understanding of genetic, epigenetic and transcriptional changes resulting in cancer progression and their relationship with treatment sensitivity.. The 4-thiazolidinone nucleus possesses marked anticancer potential towards different biotargets, thus targeting different cancer types like breast, prostate, lung, colorectal and colon cancers, renal cell adenocarcinomas and gliomas. Therefore, conjugating the 4-thiazolidinone scaffold with other promising moieties or directing the therapy towards targeted drug delivery systems like the use of nanocarrier systems, can provide the gateway for optimizing the anticancer efficiency and minimizing the adverse effects and drug resistance development, thus providing stimulus for personalized pharmacotherapy.. An exhaustive literature survey has been done to give an insight into the anticancer potential of the 4- thiazolidinone nucleus either alone or in conjugation with other active moieties, with the mechanisms involved in preventing proliferation and metastasis of cancer covering a vast range of publications of repute.. This review aims to summarise the work reported on anticancer activity of 4-thiazolidinone derivatives covering various cancer biomarkers and pathways involved, citing the data from the year 2005 till now, which may be beneficial to the researchers for future development of more efficient 4-thiazolidinone derivatives.

Topics: Antineoplastic Agents; Biomarkers; Humans; Neoplasms; Thiazolidines

Currently, cancer and its progression to metastasis result in a large number of deaths. The lack of new drugs, appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are the major obstacles in metastasis prevention and treatment. On the other hand, thiosemicarbazones and their bioisosteres, thiazole and thiazolidinone are recurring in a wide range of biologically active compounds that reach different targets within tumor context and represent a promising start point to access potential candidates in metastatic cancer. Therefore, the search for new lead compounds showing highest anticancer potency and less adverse effects is the major challenger in drug discovery. The search was based from 1994 to 2018, focusing on thiosemicarbazone, thiazole and thiazolidinone cores that allowed us to discuss how the three multi-target motifs have been used for the target-based design and development of anticancer agents. In the lasts years, thiosemicarbazone, thiazole, and thiazolidinone cores are recurrent in many approaches for cancer therapy. In our search, it was verified that due to its biodiversity and versatility the anticancer potential of such structures has been assigned to distinct mechanisms reinforcing the value of these cores in the anticancer drug development. The present article aims point out the current application of thiosemicarbazone, thiazole and thiazolidinone cores in the design of anticancer agents within tumor progression, acting via varied targets such as cathepsins, NDRG1 gene and kinases, showing in vitro tests, in vivo tests and clinical trials. In our search it was possible to verify that thiazole is the most studied and the most important of the three structures. Therefore, we hope to provide new insights and valuable inspiration in the research of new drugs and development and contribute to the management of cancer.

Topics: Animals; Antineoplastic Agents; Cell Cycle Proteins; Disease Progression; Drug Delivery Systems; Drug Discovery; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Thiazoles; Thiazolidines; Thiosemicarbazones

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

Topics: A549 Cells; Anti-Bacterial Agents; Antineoplastic Agents; Apoptosis; Caco-2 Cells; Cell Line, Tumor; Humans; Neoplasms; Pseudomonas aeruginosa; Pseudomonas Infections; Thiazolidines

PPARγ regulate the expression of genes involved in peripheral insulin sensitivity, adipogenesis, and glucose homeostasis. Moreover, PPARγ agonists, such as pioglitazone and rosiglitazone, are used in the treatment of various diseases, e.g. diabetes (type II), atherosclerosis, inflammatory skin disease, and some types of cancers. PPARγ agonists have also been found to reduce oxidative-stress (OS) and OS-induced apoptosis. Therefore, the aim of the present study was to evaluate the impact of 4-thiazolidinone-based derivatives Les-2194, Les-3377, and Les-3640 on the expression of antioxidant enzymes in human squamous cell carcinoma (SCC-15), lung carcinoma (A549), colon adenocarcinoma (CACO-2), and skin fibroblast (BJ) cell lines. After 24 h of exposure, Les-2194 caused an increase in ROS production in the SCC-15 and CACO-2 cell lines; however, no changes in caspase-3 activity and metabolic activity were observed. Nevertheless, the Ki67 level was significantly decreased. Les-3377 was able to increase ROS production in all tested cell lines, but no impact on metabolic activity and caspase-3 activity were noticed. In turn, Les-3640 was able to induce ROS overproduction in BJ, SCC-15, and CACO-2 and did not affect metabolic activity. However, an increase in caspase-3 activity was observed at the 10 µM concentration in all tested cell lines. All tested compounds were able to influence CAT and SOD1 expression and decreased (Les-2194 in the BJ cells) or increased (Les-3640 in the SCC-15 and CACO-2 cells) PPARγ expression.

Topics: A549 Cells; Antioxidants; Apoptosis; Caco-2 Cells; Caspase 3; Cell Line; Cell Line, Tumor; Humans; Neoplasms; Oxidative Stress; Pioglitazone; PPAR gamma; Reactive Oxygen Species; Rosiglitazone; Thiazolidines

To synthesize a series of new thiazolidinone-pyrazole hybrids (5a-o) and assess their anticancer (in vitro and in vivo) and antimicrobial activities.. The compounds 5h (against Ehrlich ascites carcinoma cells), 5e and 5i (against the human breast cancer [MDA-MB231] cell line) exhibited potent anticancer activity. All the compounds except 5g and 5e found to be less toxic for the human dermal fibroblast cells. The effective interactions of the compounds in silico with MDM2 exemplified their inhibitory potency. The derivatives also showed moderate antimicrobial activity.. The halogen atoms on various positions of the N-arylamino ring played an advantageous role in elevating the potency of the molecules. Thus, these conjugates could be used as a lead for further optimization to achieve promising therapeutics.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Bacteria; Bacterial Infections; Candida albicans; Candidiasis; Cell Line, Tumor; Cell Survival; Humans; Mice; Molecular Docking Simulation; Neoplasms; Proto-Oncogene Proteins c-mdm2; Pyrazoles; Structure-Activity Relationship; Thiazolidines