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Eleven new steroidal mono- and bis(semicarbazones)2a–e, 4d and 3a–e have been prepared starting from various 3-oxo-α,β-unsaturated steroids. Mono-semicarbazones 2a–e were further subjected to ethyl chloroacetate in boiling absolute ethanol but, instead of expected intramolecular cyclocondensation reaction products, the new carbazate esters 5a-e were obtained. The structures of all synthesized compounds and identification of each E/Z isomer were deduced by elemental analysis, HRMS, NMR, and IR spectroscopy. Preliminary screening for the cytotoxic activity in vitro of the new compounds has been conducted against three cancer cell lines, K562, Jurkat and HeLa cells. HeLa cells were the most sensitive while K562 cells were the least sensitive to the cytotoxic action of the novel steroid derivatives. Compounds 2e, 3c and 5e were found to have the best but still moderate cytotoxic effects. All tested compounds showed very weak antimicrobial activities. These results demonstrate that the replacement of thioxo group with carbonyl group in steroidal hydrazone derivatives resulted in decrease in their biological activity.

The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (5)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC50 values from 8.5 mu M to 14.9 mu M), eight on HeLa cells (IC50 values ranging from 8.9 mu M to 15.1 mu M) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC50 values from 12.7 mu M to 25.6 mu M) than cisplatin (21.5 mu M) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activ

A series of new steroidal mono- and bis(thiosemicarbazones) (2a-e and 3a-e) and corresponding mono- and bis(1,3,4-thiadiazolines) (4a-e and 5a-e) was synthesized, characterized and evaluated for their anticancer activity. Detailed NMR analysis of the mono-and bis(thiosemicarbazones) revealed the presence of two stereoisomers (Z and E) with different configurations in the hydrazone moiety at the C-3 position, where the substituents on the C(3)]=N double bond in the main isomers adopted the E configuration. The configurations at C-3 and C-17 in thiadiazolines 4a-e and 5a-e were deduced by detailed NMR analysis as well as by the examination of Dreiding molecular models and X-ray analysis of 3-thiadiazoline 4a, which confirmed the structure and absolute configuration at C-3. The synthesized compounds were tested against six cancer cell lines (HeLa, K562, MDA-MB-361, MDA-MB-453, LS174 and A549), the normal human cell line MRC-5 and peripheral blood mononuclear cells (PBMC) isolated from healthy donors. The best activity was exhibited by 3-thiosemicarbazones 2a, 2b, 2c and 2e and 3,17-bis(thiadiazolines) 5a and 5d. Examination of the mechanisms of cytotoxicity on cervical adenocarcinoma HeLa cells revealed the pro-apoptotic action of these compounds, which triggered both extrinsic and intrinsic apoptotic pathways. These compounds also showed the ability to decrease angiogenesis in vitro. In addition, 3,17-bis(thiadiazolines) 5a and 5d showed high selectivity in anticancer activity against all the examined malignant cell lines. Compound 5a displayed prominent anticancer potential. The tested compounds showed poor antimicrobial activity.

Square-planar isocyanate and chloride Ni(II) complexes with tridentate PNO condensation product of 2-(diphenylphosphino)benzaldehyde and Girard’s T reagent have been synthesized and their crystal structures determined. These Ni(II) complexes with different monodentate ligands, chloride, cyanate and thiocyanate, were tested for their antimicrobial activities against pathogenic microorganisms. The ligand and Ni(II) complexes were active not only against laboratory control strains of bacteria and yeast, but also on clinical isolates of E. coli and P. aeruginosa strains resistant to most of the clinically used antibiotics.

Square-planar isocyanate and chloride Ni(II) complexes with tridentate PNO condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent have been synthesized and their crystal structures were determined. These Ni(II) complexes with different monodentate ligands, chloride, cyanate, and thiocyanate were tested for their antimicrobial activities against pathogenic microorganisms. The ligand and Ni(II) complexes were active not only against laboratory control strains of bacteria and yeast, but also on clinical isolates of Escherichia coli and Pseudomonas aeruginosa strains resistant to most of the clinically used antibiotics.

The in vitro cytotoxic activity of previously synthesized steroid dimers with different spacer group (sulfide, trithiolane ring or phosphorotrithioate) and the substituent at C-17 position was tested for their possible effects against following human tumor cell lines: cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562) and two human breast cancer cell lines (MDA-MB-361 and MDA-MB-453). These compounds, applied at micromolar concentrations, exhibited cytotoxic activity of different intensity (compared with cisplatin as a control), modality and selectivity in these malignant cell lines. The best activity against all four cell cancer lines was exhibited by dimer-sulfides. All screened compounds exerted concentration-dependent cytotoxic activity against leukemia K562 cells. The compounds which exerted the most pronounced cytotoxic action exhibited notably higher cytotoxic activities against K562, HeLa and MDA-MB-453 cells in comparison to resting and PHA-stimulated PBMC, pointing to a significant selectivity in their antitumor actions. Examination of the mechanisms of cytotoxicity on leukemia K562 cells revealed pro-apoptotic action of each of the investigated compounds applied at concentrations 2IC(50). The most prominent pro-apoptotic action was exhibited by dimer-sulfide of cholest-4-en-3-one. Furthermore, almost all of the tested compounds at IC50 concentrations induced G1 phase cell cycle arrest in K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia sauna, were evaluated. There was no antibacterial activity. The best antifungal activity was exhibited against Saccharomyces cerevisiae by dimers linked with trithiolane ring, indicating a selective activity of investigated compounds. (C) 2014 Elsevier Ltd. All rights reserved.

Complexes of Pd(II) and Fe(III) with the condensation derivative of 2-(diphenylphosphino)benzaldehyde and ethyl carbazate were synthesized, characterized, and their antimicrobial activity was evaluated. The structures of the Pd(II) and Fe(III) complexes in solid state were determined by IR, elemental analysis and X-ray analysis. The structure of Pd(II) complex in solution was determined by NMR spectroscopy. Results of magnetic measurements for Fe(III) complex were reported. In both complexes the ligand is coordinated as tridentate via the phosphorus, the imine nitrogen and the carbonyl oxygen atoms. Results of antimicrobial activity investigation indicate that the activity of the ligand is enhanced upon complexation, and that the MIC values of the iron complex to some bacterial strains are not much higher than those of cefotaxime. (C) 2014 Elsevier Ltd. All rights reserved.