Diana Wesselinova

Antitumour activity of novel 1,10-phenanthroline and 5-amino-1,10-phenanthroline derivatives

Synthesis and impact on the tumour growth of palladium(II) complex of 5-amino-1,10-phenanthroline Pd(5-NH(2)-phen)(2)(NO(3))(2) and the protonated dimer (phen)(2)(H(+))(BF(4)(-)) have been described. In the reported experiments a cancerous (100% lethality) myeloid subcutaneous tumour (with Graffi-tumour origin) in hamsters was used. The animals were injected i.p. with different doses of the substances. The longest mean survival time (1.65 times longer than the controls) was achieved when the substance Pd(5-NH(2)-phen)(2)(NO(3))(2) was injected into the animals. One of the animals even survived until the 71st day, which is 2.2 times longer than the controls. The compound (phen)(2)(H(+))(BF(4)(-)) prolonged the mean life-time of the animals 1.4 times in comparison to the controls. On the other hand, the Pd(II) complex of 1,10-phenanthroline, Pd(phen)(2)(H(2)O)(NO(3))(2), did not reveal any antitumour activity. Our experience concerning the effect of other drugs on this tumour has shown a survival time no longer than 4-5d after the death of the controls.

Cytotoxicity and effects of 1,10-phenanthroline and 5-amino-1,10-phenanthroline derivatives on some immunocompetent cells

The biological activity of previously synthesized compounds [(phen)(3)(H(+))(2)(NO(3)(-))(2) (1), Pd(5-NH(2)-phen)(2)(NO(3))(2) (2) and Pd(phen)(2)(NO(3))(2)(H(2)O) (3)] was investigated in vivo. The three compounds did not show any histological alterations in the observed lung, liver, spleen and lymph nodes of White Wistar rats. The propidium iodine staining did not discover any cytotoxic effect of the tested derivatives. The tests for immunological response predominantly showed stimulation of the antibody-producing B-cells and lower or no stimulation of the T-cells. The LIF-test showed better stimulation of all lymphocytes with 1, followed by 2 and 3. Substance 3 showed highest stimulating effect on B-cell blood lymphocytes in all doses (maximum in the lowest dose), whereas the impact of 2 is weaker and that of 1 is the weakest. The T-cell immune response after treatment with substance 1 is best influenced by dose of 1mg in the spleen cell-fraction, followed by 3 (5 mg).

Self-assembly of novel molecular complexes of 1,10-phenanthroline and 5-amino-1,10-phenanthroline and evaluation of their in vitro antitumour activity

Novel molecular complexes of 1,10-phenanthroline (phen) and 5-amino-1,10-phenanthroline (5-NH2-phen) [(5-NH2-phen)2(phen) (H2O)3 (1), (phen)2(imidazole) (H+) (BF4-) (2), (phen)2(benzimidazole) (H+) (BF4-) (3), (5-NH2-phen)4(H2O)3 (4), and (phen)3 (indole) (H+) (BF4-) (5)] were synthesized via self-assembly processes and their in vitro anticancer activity was investigated. The structures of the compounds were confirmed by UV, FTIR, CIMS(CH4) and elemental analysis. The crystal structure of 2 was determined by X-ray diffraction. Cytotoxicity of the substances was measured using the cultivated human tumour cell lines HepG2, HEp-2, and 8-MB-GA. The tested substances showed different activity depending on the cell line and amount used. Substances 2 and 3 were not toxic to the non-tumour cells (Lep-3), but significantly toxic to all tumour ones. This is not the case with compounds 4 and 5, which are non-toxic towards carcinogenic cell lines, but even stimulate both HepG2 and HEp-2.

Synthesis and biological activity of novel heavy metal complexes of 5-amino-1, 10-phenanthroline and 1,10-phenanthroline

AbstractNovel heavy metal complexes: Sr(5-NH2-phen)4(NO3)(OH)(H2O)2 (1) (synthesized via a static self-assembly process) and Sn(phen)(NO3)(OH)(H2O) (2), Sn(5-NH2-phen)(OH)(Cl)(H2O) (3), Pb(5-NH2-phen)(NO3)2(H2O) (4) (obtained via metal competitive reactions under mild conditions) were reported. The coordination compounds were characterized by elemental analysis, FTIR-spectroscopy and FAB-mass spectrometry. Their cytotoxicity was measured by MTS-test towards human tumour (MDA-MB-231, HT-29, HeLa, HepG2) and non-tumour diploid (Lep-3) cell lines. The most pronounced cytotoxic effect on all cancer lines showed 1 and 4 at their high concentrations as well as 1 at its lower ones (≤ 4×10−2 mg). Therefore, strontium complex of 5-amino-o-phenanthroline (1) exhibited the widest antitumour spectrum activity, having no toxicity to non-tumour cells at quantities ≤ 4×10−2 mg. The computed EC50 values of 1–4 against MDA-MB-231, HT-29, HeLa, HepG2 varied from 1.40×10−3 to 6.31×10−6 M. Towards Lep-3 substances 2–4 showed IC50 7.52×10−4 − 0.44 M. Substance 1 possess EC50=1.26×10−7 M to the non-tumour cells.

Synthesis, Cytotoxicity And Antioxidant Activity Of New Analogues Of Rc-121 Synthetic Derivatives Of Somatostatin.

BACKGROUND Based on the structure of RC-121 (D-Phe-c (Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2, - synthetic derivatives of somatostatin), some analogs were synthesized and tested for in vitro cytotoxic and antioxidant activity. OBJECTIVES The new analogs were modifyed at position 5 with Dap (diaminopropanoic acid), Dab (diaminobutanoic acid) and Orn and at position 6 with the unnatural amino acids Tle (t-leucine). METHODS The in vitro cytotoxic effects of the substances were investigated against a panel of human tumor cell lines HT-29 (Human Colorectal Cancer Cell Line), MDA-MB-23 (Human Breast Cancer Cell Line), Hep G-2 (Human Hepatocellular Carcinoma Cell Line) and HeLa (cervical cancer cell line). The antioxidant capacities were tested by ORAC (Oxygen Radical Antioxidant Capacity) and HORAC (Hydroxyl Radical Averting Capacity) methods. RESULTS All substances expressed significantly higher antioxidant capacity by comparison with galic acid and Trolox. All substances showed considerable antioxidant capacity as well. Compound 2T (D-Phe-c(Cys-Tyr-DTrp- Dap-Tle-Cys)-Thr-NH2)had the highest antioxidant effect. The compound 4T (D-Phe-c(Cys-Tyr-D-Trp- Orn-Tle-Cys)-Thr-NH2) displayed antiproliferative effect on HeLa cells with IC50 30 µM. The peptide analog 3T (D-Phe-c(Cys-Tyr-D-Trp-Lys-Tle-Cys)-Thr-NH2) exerted the most pronounced inhibition on the cell vitality up to 53%, 56% and 65% resp. against MDA-MB-23, Hep G-2, HeLa in the higher tested concentration. CONCLUSION The somatostatin analogs showed moderate influence on the vitality of different tumor cells and could be used in changing their pathology.