Sixteen hydrazinyl-thiazolo arene ruthenium complexes of the general formula [(η⁶-p-cymene)Ru(N,N′-hydrazinyl-thiazolo)Cl]Cl were synthesized. All complexes were tested in vitro for their antiproliferative activity on three tumor cell lines (HeLa, A2780, and A2780cisR) and on a noncancerous cell line (HFL-1). A superior cytotoxic activity of the ruthenium complexes as compared to cisplatin and oxaliplatin, on both cisplatin-sensitive and cisplatin resistant ovarian cancer cells, was observed. In addition, the biological activity of two selected derivatives was evaluated using microarray gene expression assay and ingenuity pathway analysis. p53 signaling was identified as an important pathway modulated by both arene ruthenium compounds. New activated molecules such as FAS, ZMAT3, PRMT2, BBC3/PUMA, and PDCD4, whose overexpressions are correlated with overcoming resistance to cisplatin therapy, were also identified as potential targets. Moreover, the arene ruthenium complexes can be used in association with cisplatin to prevent cisplatin resistance development and synergistically to induce cell death in ovarian cancer cells.

Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC₅₀: 11.6 μM (1), and 12.4 μM (3)] and HeLa [IC₅₀: 22.4 μM (1) and 19.4μM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)³⁺ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals.

New and known arylidene-hydrazinyl-thiazole derivatives have been synthesized by a convenient Hantzsch condensation. All compounds were evaluated for their in vitro cytotoxicity on two carcinoma cell lines, MDA-MB231 and HeLa. Significant antiproliferative activity for 2-(2-benzyliden-hydrazinyl)-4-methylthiazole on both MDA-MB-231 (IC₅₀: 3.92 µg/mL) and HeLa (IC₅₀: 11.4 µg/mL) cell lines, and for 2-[2-(4-methoxybenzylidene) hydrazinyl]-4-phenylthiazole on HeLa (IC₅₀: 11.1 µg/mL) cell line is reported. Electrophoresis experiments showed no plasmid DNA (pTZ57R) cleavage in the presence of the investigated thiazoles.

In the context of there being a limited number of clinically approved drugs for the treatment of Candida sp.-based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-Candida potential. Two compounds (7a and 7e) showed promising inhibitory activity against the pathogenic C. albicans strain, exhibiting substantially lower MIC values (7.81 μg/mL and 3.9 μg/mL, respectively) as compared with the reference drug fluconazole (15.62 μg/mL). Their anti-Candida activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound 7e with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.

Inflammation and hyperlipidemia play an essential role in the pathophysiology of endothelial dysfunction as well as atherosclerotic plaque formation, progression and rupture. Colchicine has direct anti-inflammatory effects by inhibiting multiple inflammatory signaling pathways. The purpose of our study was to evaluate colchicine activity in an animal model of hyperlipidemia induced by diet. A total of 24 male rats (wild type, WT) were divided into three groups: group one fed with a basic diet (BD) (WT + BD, n = 8), group two fed with a high-fat diet (HFD) (WT + HFD, n = 8)), and group three which received HFD plus drug treatment (colchicine, 0.5 mg/kg, i.p., daily administration). Total cholesterol, LDL-, HDL-cholesterol and triglycerides were determined. In addition, plasma transaminases, inflammation of oxidative stress markers, were measured. Tissue samples were evaluated using hematoxylin-eosin and red oil stain. At the end of the study, rats presented increased serum lipid levels, high oxidative stress and pro-inflammatory markers. The aortic histopathological section revealed that HFD induced signs of endothelial dysfunction. Colchicine treatment significantly resolved and normalized these alterations. Moreover, colchicine did not influence NAFLD activity score but significantly increased ALT and AST levels, suggesting that colchicine amplified the hepatocellular injury produced by the diet. Colchicine reduces plasma lipid levels, oxidative stress and inflammation markers and leads to more favorable histopathologic vascular and cardiac results. However, the adverse effects of colchicine could represent an obstacle to its safe use.

The molecular frame of the reported series of new polyheterocyclic compounds was intended to combine the potent phenothiazine and benzothiazole pharmacophoric units. The synthetic strategy applied was based on oxidative cyclization of N-(phenothiazin-3-yl)-thioamides and it was validated by the preparation of new 2-alkyl- and 2-aryl-thiazolo[5,4-b]phenothiazine derivatives. Optical properties of the series were experimentally emphasized by UV-Vis absorption/emission spectroscopy and structural features were theoretically modelled using density functional theory (DFT). In vitro activity as antileukemic agents of thiazolo[5,4-b]phenothiazine and N-(phenothiazine-3-yl)-thioamides were comparatively evaluated using cultivated HL-60 human promyelocytic and THP-1 human monocytic leukaemia cell lines. Some representatives proved selectivity against tumour cell lines, cytotoxicity, apoptosis induction, and cellular metabolism impairment capacity. 2-Naphthyl-thiazolo[5,4-b]phenothiazine was identified as the most effective of the series by displaying against THP-1 cell lines a cytotoxicity close to cytarabine antineoplastic agent.