Miloš V. Nikolić

Synthesis and Characterization of Zinc(II)-Complexes with S-Alkyl Derivatives of Thiosalicylic Acid

Abstract New zinc(II)-complexes with S-alkyl derivatives of thiosalicylic acid (alkyl = benzyl-(L1), methyl-(L2), ethyl-(L3), propyl-(L4), butyl-(L5)) have been synthesized and characterized by elemental microanalysis, IR spectroscopy, and 1H and 13C NMR spectroscopy. The S-alkyl derivatives of thiosalicylic acid were prepared by alkylation of thiosalicylic acid by adding alkyl halides to an alkaline water-ethanol solution, while the corresponding zinc(II)-complexes were obtained via the direct reaction of ZnCl2 with S-alkyl derivatives of thiosalicylic acid in water. Based on the microanalysis results and the IR and NMR spectra of the S-alkyl derivatives of thiosalicylic acid and the corresponding zinc(II)-complexes, we concluded that the ligands are bidentately coordinated to the zinc(II)-ion.

Synthesis and Characterization of Platinum (IV) complexes with S-alkyl Derivatives of Thiosalicylic Acid and the Crystal Structure of the S-butyl Derivative of Thiosalicylic Acid

Abstract New platinum(IV)-complexes with S-alkyl derivatives of thiosalicylic acid (alkyl = benzyl-(L1), methyl-(L2), ethyl-(L3), propyl-(L4), butyl-(L5)) have been synthesized and characterized by microanalysis, infrared spectroscopy, and 1H and 13C NMR spectroscopy. Th e bidentate S,O ligand precursor, the S-butyl derivative of thiosalicylic acid (S-bu-thiosal), was prepared, and its crystal structure was determined. Single crystals suitable for X-ray measurements were obtained by slow crystallization from a DMSO-water system. S-bu-thiosal crystallized in a P21/c space group of a monoclinic crystal system with a = 8.0732 (3) Å, b = 19.6769 (4) Å, c = 8.2291 (3) Å and Z = 4. S-bu-thiosal also has a coplanar geometry.

DNA binding and antitumor activities of platinum(IV) and zinc(II) complexes with some S-alkyl derivatives of thiosalicylic acid

A series of complexes of platinum(IV) (C1–C5) and zinc(II) (C6–C10) with S-alkyl derivatives of thiosalicylic acid were prepared and characterized. The interactions of the complexes with calf thymus DNA were analyzed by absorption (UV–Vis) and emission spectral studies (ethidium bromide displacement studies). The cytotoxic activities of complexes C1–C10 were determined against mouse B cell lymphocytic leukemia cells (BCL1), human B-prolymphocytic leukemia (JVM-13), mouse mammary carcinoma cells (4T1), and human mammary carcinoma cells (MDA-MB-468) and compared to the activities of the free ligand precursors and cisplatin. The cytotoxicities of the platinum(IV) and zinc(II) complexes toward mouse tumor cell lines were higher compared with their effects on human tumor cell lines. The zinc(II) complex C9 showed the highest antitumor activity toward the tested human cell lines, while the platinum(IV) complex C4 exhibited the highest antitumor activity toward mouse BCL1 and 4T1 cells. Both C4 and C9 have ligands derived from S-propyl thiosalicylic acid.

Synthesis, Characterization, and Cytotoxicity of Binuclear Cooper(II)-Complexes with some S-Alkenyl Derivatives of Thiosalicyclic Acid

Abstract New complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (alkenyl = propenyl-(L1), isobutenyl-(L2)) have been synthesized and characterized by microanalysis, infrared spectra, magnetic measurements, and by NMR spectra. The cytotoxic activity of two newly synthesized precursor S-alkenyl derivatives of thiosalicylic acid were tested using an MTT colorimetric technique on HCT-116 human colon carcinoma cells. The cytotoxic effect of the copper(II)- complexes were higher compared to the cytotoxicity of the corresponding ligand (for concentrations from 31.25 to 250 μM). Copper(II)-complexes showed a slightly lower cytotoxicity compared to cisplatin. Complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (at concentrations from 250 to 1000 μM) had a cytotoxic effect on HCT-116 cells compared to cisplatin.

Antibacterial and antibiofilm screening of new platinum(IV) complexes with some s-alkyl derivatives of thiosalicylic acid

The influence of 5 new Platinum(IV) (Pt(IV)) complexes with S-alkyl derivatives of thiosalicylic acid (C1-benzyl, C2-methyl, C3-ethyl, C4-propyl and C5- butyl) was studied on 16 strains of bacteria. Antibacterial activity was tested using microdilution method with resazurin while antibiofilm activity was observed by tissue culture plate method, using doxycycline as a positive control. The results were expressed as minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and biofilm inhibitory concentration (BIC). The best result on Gram positive bacteria exhibited C1 and MIC was <7.81μg/ml against Staphylococcus aureus ATCC 25923. Bifidobacterium animalis subsp. lactis (probiotic) was sensitive to C2 (MIC at 15.625 μg/ml). The highest sensitivity of Gram negative bacteria was observed in Escherichia coli ATCC 25922 treated with C1, C2, C3 and C4, in Proteus mirabilis ATCC 12453 treated with C1, and in Pseudomonas aeruginosa treated with C2, C3 and C5 (all MICs at 250 μg/ml). The C2 complex were more efficient as antibiofilm agents and the best results were obtained with C2 acting against S. aureus and S. aureus ATCC 25923 biofilms. In conclusion, we noticed that the tested compounds exhibited promising properties as antibacterial and antibiofilm agents.

Factors Influencing the Fear of Needles among Students of Medicine and Pharmacy

Summary Fear of needles can significantly limit professional and social functioning of a person, and is highly prevalent in general population (4%). The aim of our study was to reveal risk factors that are associated with fear of needles among healthy university students of medicine and pharmacy. The study was of a cross-sectional type. In total, 301 students of medicine or pharmacy (82% female and 18% male) attending from 1st to 5th year of study were surveyed at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The students were surveyed using a questionnaires (scales) for assessing the fear of needless, a visual analog scale for self-assessment intensity of the fear of needless, and a general questionnaire with questions about socio-demographic characteristics of the participants. Using a score on the scales as out-come variables, multiple regressions were employed to reveal factors that may influence the fear of needles. Average values of Blood/Injection Fear Scale, Injection Phobia Scale-Anxiety and Medical Avoidance Survey scores were 7.89 ± 9.48, 4.46 ± 5.18 and 89.95 ± 12.73, respectively. The following factors affected significantly the score of the scales: course of study, chronic disease in the family, fear of a dentist, smell of the room phobia, sound phobia, score on the Beck’s anxiety scale and fear of a situation when medical staff give an injection. The presence of chronic disease in the family was a protective factor, while the other six factors were contributing to the fear of needles. Fear of needles is more prevalent among the students of pharmacy than among the students of medicine. It is less frequent among students with chronic disease in their family, while fear of dentist, smell of the room phobia, sound phobia, general anxiety and fear from the situation when medical staff give an injection are all factors that predispose students of medicine or pharmacy to develop fear of needles.