No abstract

Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 (CYP) enzymes play a major role in the activation of these chemicals. Using highly specific and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. the expression profile of all major xenobiotic metabolizing CYP forms was screened in breast tumour and surrounding tumour free (control) breast tissue in a series of 20 sample pairs obtained from females with infiltrating ductal carcinoma. The levels of CYPIAI mRNA were very low in both tumour and normal tissue. CYP1B1, CYP2B6, CYP2C, CYP2D6, CYP2E1, CYP4B1, and CYP11A1 expressions were positive in both tumours and control tissue. CYP2A6, CYP2A7, CYP2A13, CYP2F1, CYP3A4, CYP3A5. and CYP3A7 mRNAs were expressed neither in tumours nor in control tissue. These results show that several CYPs. responsible for the activation of a quite large number of procarcinogens and genotoxic estrogen metabolites. are expressed in breast tissue with a lack of qualitative differences in CYP expression at mRNA level between breast tumours and surrounding normal breast.

Some novel benzimidazole derivatives carrying thiosemicarbazide and triazole moieties at the N1 position were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels determined by measuring the formation of 2-thiobarbituric acid reactive substance. The free radical scavenging properties of the compounds were also examined in vitro by determining the capacity to scavenge superoxide anion formation and the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The compounds showed a significant effect in the above tests except to scavenge superoxide anion formation.

Aromatic ester derivatives of ferulic acid where the phenolic hydroxyl is free (6a-d) or acetylated (5a-d) were evaluated for their antioxidant and antimicrobial properties. The superoxide radical scavenging capacity of compounds 5d and 6d-e (IC(50) of 0.19, 0.27 and 0.20 mM, respectively) was found to be twice as active as α-tocopherol (IC(50) = 0.51 mM). DPPH radical scavenging capacity was moderate and only found in compounds bearing free phenolic hydroxyl groups (6a-e). With regard to antimicrobial properties, compounds 6b and 6c displayed significant activity against Enterococcus faecalis (MICs = 16 μg/mL) and vancomycin-resistant E. faecalis (MIC for 6b, 32 and for 6c, 16 μg/mL). Compound 6c also demonstrated prominent activity against planktonic Staphylococcus aureus with a MIC value of <8 μg/mL and it inhibited bacterial biofilm formation by S. aureus with a MBEC value of <8 μg/mL, which was 64 and 128 times more potent than ofloxacin and vancomycin, respectively.

Some 6-fluoro-5-substituted-benzimidazole derivatives in which indole and 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene groups were attached to the 2-position of the benzimidazole ring were synthesized and tested for antioxidant properties in vitro. Almost all the synthesized compounds at the 10(-3) M concentrations showed superoxide anion scavenging activity. Compounds 5, 3, 9, 4, 17 and 13 have strong inhibitory effects on superoxide anion formation (98%, 93%, 91%, 88%, 85% and 81%, respectively) at 10(-3) M concentration and these results are better than 30 IU of superoxide dismutase (SOD) (76%). Compound 11 is the most effective scavenger of 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable free radical at 10(-3)M (61%) concentration.