New Metastable Baro- and Deformation-Induced Phases in Ferromagnetic Shape Memory Ni2MnGa-Based Alloys.

Structural and phase transformations in the microstructure and new metastable baro- and deformation-induced phases of the Ni50Mn28.5Ga21.5 alloy, typical of the unique class of ferromagnetic shape memory Heusler alloys, have been systematically studied for the first time. Phase X-ray diffraction analysis, transmission and scanning electron microscopy, and temperature measurements of electrical resistivity and magnetic characteristics in strong magnetic fields were used. It was found that in the course of increasing the pressure from 3 to 12 GPa, the metastable long-period structure of martensite modulated according to the 10M-type experienced transformation into a final non-modulated 2M structure. It is proved that severe shear deformation by high pressure torsion (HPT) entails grainsize refinement to a nanocrystalline and partially amorphized state in the polycrystalline structure of the martensitic alloy. In this case, an HPT shear of five revolutions under pressure of 3 GPa provided total atomic disordering and a stepwise structural-phase transformation (SPT) according to the scheme 10M → 2M → B2 + A2, whereas under pressure of 5 GPa the SPT took place according to the scheme 10M → 2M → B2 → A1. It is shown that low-temperature annealing at a temperature of 573 K caused the amorphous phase to undergo devitrification, and annealing at 623-773 K entailed recrystallization with the restoration of the L21 superstructure in the final ultrafine-grained state. The size effect of suppression of the martensitic transformation in an austenitic alloy with a critical grain size of less than 100 nm at cooling to 120 K was determined. It was established that after annealing at 773 K, a narrow-hysteresis thermoelastic martensitic transformation was restored in a plastic ultrafine-grained alloy with the formation of 10M and 14M martensite at temperatures close to those characteristic of the cast prototype of the alloy.

Novel lipophilic 7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid derivatives as potential antitumor agents: improved synthesis and in vitro evaluation.

A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC(50) values in the 0.2-2.2 µM range, while IC(50) values for parent LV ranged between 70 and 622 µM depending on the cell line. The esters displayed no in vivo toxicity up to 80 mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent.

7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: synthesis and in vitro biological evaluation as potential antitumor agents.

Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC(50) values ranging from microM to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC(50) values were 10 microM in three (derivative 2) or four (derivative 6h) cancer cell lines.

Synthesis of lipophilic dimeric C-7/C-7-linked ciprofloxacin and C-6/C-6-linked levofloxacin derivatives. Versatile in vitro biological evaluations of monomeric and dimeric fluoroquinolone derivatives as potential antitumor, antibacterial or antimycobacterial agents.

The synthesis of C-7/C-7-linked ciprofloxacin (CP) and C-6/C-6-linked levofloxacin (LV) derivatives with modulated lipophilicity is described herein. The synthesized compounds, along with the monomeric analogs described previously, were evaluated in vitro for (i) their growth inhibitory effect against five human cancer cell lines, (ii) their antibacterial activity against Gram-positive Staphylococcus aureus and Enterococcus hirae and Gram-negative Escherichia coli and Pseudomonas aeruginosa strains and (iii) their antimycobacterial activity. The most efficient derivatives as antiproliferative agents (C-7/C-7-linked CP 7e and C-6/C-6-linked LV 11f) displayed IC(50) values in the 0.1-8.7 and 0.2-0.7 µM ranges respectively while IC(50) values for parent CP and LV ranged from 89 to 476 µM and from 67 to 622 µM respectively depending on the cell line. A specific antibacterial activity against S. aureus was found for the monomeric and dimeric derivatives of CP. The most efficient derivative against S. aureus (monomeric oxoethyloctanoate CP derivative 3d) displayed MIC <1 nM. Monomeric alkanoyloxymethyl LV esters (9a,c,e,f) and C-6/C-6-linked LV derivatives (11f-h) were the most efficient derivatives as antimycobacterial agents with MIC and IC(50) values in the 2.5-5 µM and 1.3-≤ 2.5 µM ranges respectively while MIC and IC(50) values for parent LV were 2.5 and 0.8 µM, respectively.