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Biomedical subjects

I Niculescu-Duvăz

Publications and source records attributed to I Niculescu-Duvăz.

17 recordsLinked to original sources
PubMed1991

A new class of potential carcinogenesis inhibitors: hindered p-benzoquinones.

The investigation of the mechanisms of action by which phenolic antioxidants (i.e. BHA, BHT, etc.) protect DNA against interaction with activated BaP, led us to the finding that oxidated aminophenols are much more potent in this respect, being also powerful inhibitors of cytochrome P-450 dependent monooxygenases. However, the quinoneimine structures probably involved in this effect are chemically unstable reactive species and therefore difficult to handle. Based on these observations, we extended this study on several types of benzoquinones. We demonstrated that 2,6-di-t-butylbenzoquinone exerted a very good protective effect at DNA level (in standard conditions) as compared to the "classical" BHA (i. e. 91.3% and 34.4%, respectively). This hindered quinone is nontoxic (DL50 = 3085 mg/kg b. w.) and also did not exhibit inhibitory activity against GST. In contrast, the nonsubstituted p-benzoquinone is a powerful inhibitor of this last enzyme. Recently, 2,6-di-t-butylbenzoquinone was isolated from mutagenic depressing food and was considered one of the factors responsible for this effect.

Animals↗
PubMed1985

QSAR application in chemical carcinogenesis. II. QSAR analysis of a class of carcinogenesis inhibitor: retinoids.

Quantitative structure-activity relationships for the reversion of keratinization of hamster tracheal cell organ culture by structurally related retinoids were formulated. Their biological activities (ED50 . M) were correlated with the following parameters: the minimal topological difference (describing the fit of the considered molecules with a possible receptor site) and the lipophilicity constants. For computation purposes the retinoids were divided in three series (A, B and C) according to structural modifications in the cyclic moiety of the molecule, in the polienic chain and in the terminal functional group, respectively. The computed regression equations suggested the importance of the stereochemical features of cyclic moiety (for series A, eq. 1, n = 19, r = 0.926, F = 48.19) and of the uninterrupted conjugation for the polienic chain (for series B, eq. 6, n = 11, r = 0.954, F = 39.39) for the biological activity. In order to check the prediction potential of the regression equation computed for the overall set of compounds (eq. 10, n = 53, r = 0.853, F = 32.11), it was used to calculate the ED50 for a test series of 15 retinoids. The correlation obtained between ED50 exp and ED50 calc for this series was r = 0.916, F = 60.25. The nature of the receptor site possibly involved in the interaction with retinoids was discussed.

Animals↗
PubMed1981

A quantitative structure-activity analysis of the mutagenic and carcinogenic action of 43 structurally related heterocyclic compounds.

Quantitative structure-activity relationships for the carcinogenicity and mutagenicity (against Salmonella typhimurium his- TA98, TA100 and TA1537 strains) of 43 structurally related heterocyclic compounds were formulated. The compounds investigated belong to the following two series of congeners : (a) benzo(thio)-pyranoquinolines and (b) benzo(thio)pyranoindoles. Their biologic activities were correlated with the following parameters : (a) the minimal topological difference (describing the fit of the considered molecules with a possible receptor, enzyme or DNA) and (b) the lipophilicity constants. The computed regression equations suggest that the structural requirements for carcinogenicity are different from those responsible for mutagenicity in the Ames test.

Carcinogens↗
PubMed1980

Potential anticancer agents. XX. 1. Steric fit analysis in aromatic nitrogen mustards area.

A series of 31 aromatic nitrogen mustards was treated by means of the Minimal Tropological Difference (MTD)-receptor site mapping procedure by respect to toxicity (LD50) and efficacy (TGI%) against Jensen sarcoma. The correlation equations obtained for the two cases are: (Formula: see text), The low correlation coefficients indicate a not too high dependence upon steric factors of TGI% and LD50. However these results suggested that: a) the ortho-substitution represents a favorable event for both toxicity and antitumor effectiveness (j = 1 and 18 being good vertices in both corresponding hypermolecules), b) despite this effect, the steric features involved in these two biologic parameters seems to be different.

Animals↗
PubMed1980

Potential anticancer agents. XX. 2. Quantitative structure--activity relationships (QSAR) in aromatic nitrogen mustards area.

Quantitative structure--activity relationships have been fomulated for 27 aromatic nitrogen mustards derived from benzoic acids (9 monosubstituted and 18 disubstituted derivatives). Their toxicity (LD50) and antitumor activity against Jensen sarcoma were correlated with hydrolysis rate (log k66) lipophilicity constants (pi) and steric parameters (MDT). The chemical reactivity of the nitrogen mustard moiety (expressed as log k66) seems to be of main importance in determining the biological properties of these derivatives. The favorable effect of ortho-substitution was pointed out. Generally these results are in good agreement with those obtained by HANSCH et al. [7] on a different series of nitrogen mustards.

Animals↗
PubMed1978

Potential anticancer agents. XVII. New developments in the benzoic acid nitrogen mustards area.

In order to obtain aromatic nitrogen mustards with improved therapeutic index against experimental neoplasms, greater than 75 new compounds were synthetized and studied. Their structure-activity relationship analysis led to the following conclusions: (a) the carboxylic group (especially when located in the meta position with respect to the nitrogen mustard group) exerts a favorable effect on the biologic properties of such compounds, probably by improving their transport characteristics; (b) a linear relationship was found between the chemical reactivity (expressed as alkylation rate, log k66) and toxicity (LD50) of 31 investigated compounds; and (c) the ortho effects also seem to be of importance in this area for a more accurate control of the nitrogen mustard activity. Other criteria (ie, log P, nucleophilicity of the target centers) involved in the rational design of aromatic nitrogen mustards are discussed. The design of new derivatives was oriented toward compounds which (a) were able to couple with selected proteins (ie, antibodies) leaving the cytotoxic moiety intact, and (b) were obtained by coupling of the 3-N,N-bis(2-chloroethyl)amino-4-methyl-benzoyl moiety with selected carriers (steroids, chromanones, etc) by way of an esteric bond.

Aminobenzoates↗
PubMedDate not supplied

Influence of 2,4,6-triamino-pyrimidyl-5-azobenzene on the activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase in cell cultures infected with herpes simplex virus type 1.

Treatment of VERO cells with 2,4,6-triamino-pyridimyl-5-azobenzene (10 gamma/ml) one hour after inoculation of herpes simplex virus type 1 limits the influence of the virus infection, consisting in the enchancement of the activities of alkaline phosphatase, acid phosphatase and LDH (especially of the latter two enzymes) and in changes in the isoenzyme patterns of acid and alkaline phosphatases and of peroxidase. In general the influence of the drug is expressed both by the fact that enzyme levels in homogenates of infected cells become closer to the values recorded in controls, and by modifications in the isoenzyme patterns altered by virus multiplication, making them more similar to those of uninfected, untreated cells.

Acid Phosphatase↗