rhodanine and Neoplasms

Rhodanine has been recognized as a privileged scaffold in medicinal chemistry due to its well-known ability to demonstrate a broad range of biological activities. The possibility of structural diversification has contributed to the significance of rhodanine structure in effective drug discovery and design. Many studies have confirmed the potential of rhodanine-derived compounds in the treatment of different types of cancer through the apoptosis induction mechanism. Furthermore, most of the rhodanine derivatives exhibited remarkable anticancer activity in the micromolar range while causing negligible cytotoxicity to normal cells. This review critically describes the anticancer activity profile of reported rhodanine compounds and the structure-activity relationships (SAR) to highlight the value of rhodanine as the core structure for future cancer drug development as well as to assist the researchers in rational drug design.

Topics: Animals; Antineoplastic Agents; Drug Design; Drug Development; Drug Discovery; Humans; Neoplasms; Rhodanine; Structure-Activity Relationship

At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have exhibited wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery. Here, we review some deadly defects of clinical medicines to the therapy of diseases and important advances on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral, antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer Disease), indicating that rhodanine heterocycle could be used as a significant pharmacophore to develop novel pharmacological active molecules. It is believed that the review is of importance for new ideas in the development of and rational designs of rhodanine-based drugs.

Topics: Alzheimer Disease; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Diabetes Mellitus; Drug Design; Humans; Hypoglycemic Agents; Neoplasms; Rhodanine

The serine/threonine Pim kinases are overexpressed in various types of solid carcinomas and hematological malignancies, and contribute to regulating cell-cycle progression and cell survival. The aim of this study was to discover a novel pan-Pim kinases inhibitor with potent anti-proliferative activities against cancer cell lines.. We screened a panel of small molecule compounds for their ability to inhibit Pim-1 kinase activity, and the hit compound was optimized using the docking analysis to Pim-1. We evaluated kinase-inhibition activities of the rationally-designed compound against Pim-1, 2, 3 and another five kinases. Furthermore, in order to characterize the cellular activities, both solid and hematological cancer cell lines treated with the compound were subjected to anti-proliferative assay, western blotting, FACS and apoptosis assays.. We discovered a pan-Pim kinases inhibitor, compound. We identified a pan-Pim kinases inhibitor, compound

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Enzyme Inhibitors; Humans; Neoplasms; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1; Rhodanine; Signal Transduction; Small Molecule Libraries

A new series of thiazolyl-2,4-thiazolidinedione / rhodanine compounds T1-T23 was synthesized and tested for their anticancer activities. Hepatocellular carcinoma cell lines were chosen due to their strong drug resistance to test the new compounds.. All compounds were synthesized via Knoevenagel Condensation reaction and thiazolidinedione ester compounds (T3,T9,T15,T20) were hydrolyzed for obtaining the acidic compounds (T6,T12,T17,T23). All compounds were firstly screened for their anticancer activity against two hepatocellular carcinoma (HCC) cell lines, Huh7 and Plc/Prf/5 (Plc) cell lines by sulforhodamine B assay. Further IC50 values were calculated for three candidates (T4, T15, T21) in five different HCC (Huh7, Plc, Snu449, HepG2, Hep3B) and one breast cancer (Mcf7) cell line.. Compounds T4, T15, T21 had very strong anticancer effects even though their 10 µM concentration in Huh7 cell line. According to IC50 values, T21 was the most effective compound with IC50 values in a range from 2 to 16 µM in 6 cancer cell lines. In terms of cytotoxicity T21 mostly affected Huh7 and interestingly it was less effective against Plc.. Considering these results it can be suggested that compounds T4, T15 and T21 may lead to the development of more potent anticancer drugs in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Inhibitory Concentration 50; Neoplasms; Rhodanine; Thiazolidinediones

Using cell based screening assay, we identified a novel anti-tubulin agent (Z)-5-((5-(4-bromo-3-chlorophenyl)furan-2-yl)methylene)-2-thioxothiazolidin-4-one (BCFMT) that inhibited proliferation of human cervical carcinoma (HeLa) (IC(50), 7.2 ± 1.8 µM), human breast adenocarcinoma (MCF-7) (IC(50), 10.0 ± 0.5 µM), highly metastatic breast adenocarcinoma (MDA-MB-231) (IC(50), 6.0 ± 1 µM), cisplatin-resistant human ovarian carcinoma (A2780-cis) (IC(50), 5.8 ± 0.3 µM) and multi-drug resistant mouse mammary tumor (EMT6/AR1) (IC(50), 6.5 ± 1 µM) cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM), BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably) state by 135% and reduced the dynamicity (dimer exchange per unit time) of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i)) of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2) at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug resistance cells by suppressing microtubule dynamics and indicated that the compound may have chemotherapeutic potential.

Topics: Animals; Calcium-Binding Proteins; Cell Cycle; Cell Cycle Proteins; Cell Death; Cell Line, Tumor; Cell Proliferation; Cyclin B1; Cyclin-Dependent Kinase Inhibitor p21; Drug Screening Assays, Antitumor; Humans; Kinetochores; Mad2 Proteins; Mice; Microtubules; Mitotic Index; Neoplasms; Polymerization; Porphobilinogen; Protein Serine-Threonine Kinases; Repressor Proteins; Rhodanine; Thiazolidines; Thiones; Tubulin; Tubulin Modulators; Tumor Suppressor Protein p53; Vinblastine

To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of the genome. The rhodanines, classified as an excellent drug scaffold, were found to be the most potent inhibitors for DNA Pol λ. Importantly, they are up to 10 times less active against the highly similar DNA polymerase β. We investigated basic structure activity relationships. Furthermore, the rhodanines showed pharmacological activity in two human cancer cell lines. So the here reported small molecules could serve as useful DNA Pol λ probes and might serve as starting point to develop novel therapeutic agents.

Topics: Antineoplastic Agents; Cell Survival; DNA Polymerase beta; Enzyme Inhibitors; Female; HeLa Cells; Hep G2 Cells; High-Throughput Screening Assays; Humans; Inhibitory Concentration 50; Models, Molecular; Neoplasms; Quantitative Structure-Activity Relationship; Rhodanine

A series of rhodanine-containing sorafenib analogs was designed, synthesized and evaluated for their in-vitro antitumor activity against three cancer cell lines (A549, H460 and HT29). Pharmacological data indicated that some of the target compounds possessed marked antiproliferative activity superior to the reference drug sorafenib, especially the most promising compound 7r (with the IC(50) value of 0.8, 1.3 and 2.8 µM against A549, H460 and HT29 cell lines, respectively). The activity was found to strongly depend on the substitution pattern of the rhodanine motif at C-5″ position. Results suggested that this series of compounds could serve as the bases for the development of novel antitumor agents.

Topics: Antineoplastic Agents; Benzenesulfonates; Cell Line, Tumor; Cell Proliferation; HT29 Cells; Humans; Inhibitory Concentration 50; Neoplasms; Niacinamide; Phenylurea Compounds; Pyridines; Rhodanine; Sorafenib; Structure-Activity Relationship

In patients with malignant tumors, autoaggression diseases and following transplantations the blood rhodanide level was found to increase; a correlation with the results of the MEM test was established.

Topics: Animals; Antibody Formation; Autoimmune Diseases; Guinea Pigs; Humans; Kidney Transplantation; Lymphocyte Activation; Macrophages; Neoplasms; Postoperative Complications; Rhodanine; Thiazoles; Transplantation, Homologous