Relationship between biological activity and dipole moment in benzo[a]phenothiazines.

Relationship between the biological activity and two different dipole moments were investigated in 9 benzo[a]phenothiazines [1-8] by calculating the dipole moment with the PM3 method. 12H-Benzo[a]phenothiazine [1], 9-methyl-12H-benzo[a]phenothiazine [2], 10-methyl-12H-benzo[a]phenothiazine[3] and 11-methyl-12H-benzo[a]phenothiazine [4] induced monocytic differentiation of human myelogenous leukemic cell lines and displayed antitumor activity. These active compounds showed a significantly smaller value of calculated ground-state dipole moment (mu g) and larger value of first excited-state dipole moment (mu e).

The in vitro antitumor assay of "half-mustard type" phenothiazines in screens of AIDS-related leukemia and lymphomas.

Twelve different "half-mustard type" phenothiazines were newly synthesized and tested on seven AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma lines; RL, KD-488, AS283, PA682 and SU-DHL-7 cell lines. The alkylene-urea substituted phenothiazines affected the growth and inhibited the growth rate of AIDS-related lymphoma cells. The Cl-substituent at the 2-position was more effective than the CF3 substitution.

The primary in vitro antitumor screening of "half-mustard type" phenothiazines.

The antitumor effects of "half-mustard type" phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures.

[Study on CAM system for dental model].

The purpose of this study was to introduce our newly-developed CAM system for dental model and to examine the shape reproducibility and measurement reliability of the CAM modelling. The system is composed of a measuring unit, which obtains three-dimensional shape information from the dental model using laser scanning, and an engineering workstation, which creates a three-dimensional graph of the dental model. Output module program which can directly process and output the three-dimensional shape data to the wide use modeling systems was developed as the software of this CAM system.

Radical modulation activity of benzo[a]phenothiazine.

12H-Benzo[a]phenothiazine generated radical(s) under alkaline conditions, and enhanced the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate. Phenothiazine and chlorpromazine hydrochloride did not produce radicals, nor affect the radical intensity of ascorbates. 12H-Benzo[a]phenothiazine scavenged the superoxide anion and hydroxyl radical, more efficiently than phenothiazine and chlorpromazine hydrochloride.

Radical intensity and differentiation-inducing activity of benzo[a]phenothiazines and phenothiazines.

ESR spectroscopy revealed that 12H-benzo [a]phenothiazine, 9-methyl-12H-benzo[a]phenothiazine, 10-methyl-12H-benzo [a]phenothiazine, 11-methyl-12H-benzo[a]phenothiazine and 5-axo-5H-benzo[a]phenothiazine, which induced the differentiation of human myelogenous leukemic cell lines into maturing macrophages, produced radical(s) under an alkaline condition. On the other hand, 6-hydroxy-5-axo-5H-benzo [a]phenothiazine, 6-methyl-5-oxo-5H-benzo[a]phenothiazine and 5H-benzo[a][1,4]benzothiazino-[3,2-c]phenothiazine, and 13 phenothiazines, which had little or no differentiation-inducing activity, produced no detectable amounts of radical(s). Using Hückel molecular orbital (HMO) method, these active benzo[a]phenothiazines were shown to have the elevated n-spin density at the sulfur atom of their molecules.

Antimutagenic effects of dehydrozingerone and its analogs on UV-induced mutagenesis in Escherichia coli.

Antimutagenic activities of dehydrozingerone, benzalacetone and its analogs substituted with the hydroxyl, methoxyl or methyl group on the benzene ring were investigated by the post-treatment for UV-induced mutagenesis in Escherichia coli WP2s (uvrA). In this assay, dehydrozingerone was a poor antimutagen. Among the test compounds except for 2-hydroxybenzalacetone, benzalacetone was the most strong antimutagen, showing that the ring substitutions decrease the antimutagenic activities.

Influence of benzo[a]phenothiazines on the element content of two tobacco tissue cultures differing in hormone requirement.

Cell proliferation and tumor formation are closely connected with hormone metabolism. We report the effect of four benzo[a]phenothiazines (12H-benzo[a]phenothiazine (1), 5-oxo-5H-benzo[a]phenothiazine (2), 10-methyl-12H-benzo[a]phenothiazine (3), and 6-hydroxy-5-oxo-5H-benzo[a]phenothiazine (4) on the growth and changes in the element compositions (Ca, Cl, Cu, I, K, Mg, Mn and Na) of auxin autotrophic and heterotrophic tobacco tissue cultures. The concentration levels of these ions were followed by means of reactor neutron activation analysis.

Relationship between resonance energy and carcinogenicity of azaarenes.

Resonance energy per pi-electron (REPE) of azaarenes were calculated by Aihara's theory of resonance energy (TRE). Consequently, it was shown that the REPE values for the cationic species not having the carbon, or nitrogen atom with the highest approximate superdelocalizability (Sr'(E)) in the parent skeleton were more unstable than those of their parent skeleton. Some correlations seem to exist between the REPE values for the cationic species not having the atom with the highest value of (Sr'(E)) in parent skeleton and carcinogenic activity.

Antimutagenicity of benzo[a]phenothiazines in chemically induced mutagenesis.

The antimutagenicity of seven benzo[a]phenothiazines was screened against Salmonella typhimurium strain TA98 treated with 4-nitro-o-phenylenediamine which is a specific mutagen to the strain, and the results were compared to the antimutagenic activity of chlorpromazine (8), one of the 2-chlorophenothiazine derivatives-which have been shown to be the most effective mutagen inhibitors. Benzo[a]phenothiazines with methyl, oxo or hydroxyl substituent(s) at position 5, 6, 9 or 10 were used in the screening tests. 6-Hydroxy-5-oxo-5H-benzo[a]phenothiazine (6) reduced the induced mutation by 27%, being a more potent antimutagenic agent than chlorpromazine (8).

Induction of a protective immunity in mice against Escherichia coli by phenothiazines, 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines and 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazines-10-yl)alkyl-1 -ureas .

Abilities of five phenothiazines, six 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines and six 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazines-10-yl)alkyl-1- ureas to induce anti-Escherichia coli activity in mice were compared. Seventeen compounds tested in this study had no antibacterial effect in direct contact with Escherichia coli using the disk diffusion method except chlorpromazine (4) with low growth inhibitory action. The pretreatment of mice with several phenothiazines, 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines or 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazines-10-yl)alkyl-1- ureas protected the animals from lethal infection of Escherichia coli to various extents.

Official multiresidue methods of pesticide analysis in vegetables, fruits and soil.

Many different types of pesticides are used extensively on fruits and vegetables. The present contribution represents an overview of the multiresidue methods of analysis of the most widely used pesticides.

Antimutagenicity of benzo[a]phenothiazines in chemically induced mutagenesis.

Antipsychotic phenothiazines are known to have antimutagenic activities. The antimutagenicity of seven Benzo[a]phenothiazines was screened against Salmonella typhimurium strain TA98 treated with 4-nitro-o-phenylenediamine (4-NPD) which is a specific mutagen to this strain, and was compared to the antimutagenic activity of chlorpromazine, a 2-chlorphenothiazine derivative which has been shown to be the most effective mutagen inhibitor in the model. Benzo[a]phenothiazines are variously substituted by methyl-, oxo- and/or hydroxyl-substituent(s) at 5, 6, 9 and/or 10 positions(s).

Decreased inositol 1,4,5-trisphosphate-specific binding in platelets from alcoholic subjects.

We measured the degree of inositol 1,4,5-triphosphate (IP3)-specific binding in platelets from alcoholic and nonalcoholic subjects. IP3-specific binding in alcoholic subjects was 45% less than that in nonalcoholic subjects. There was no significant difference in the number of IP3 receptors as detected immunologically in the platelet membrane fractions from alcoholic and nonalcoholic subjects.

Three-dimensional dental cast analyzing system using laser scanning.

The purpose of this article is to introduce the outline of our newly developed three-dimensional dental cast analyzing system with laser scanning, and its preliminary clinical applications. The system is composed of a measuring device with a slit-ray laser projector and two sets of coupled charged devised video cameras, an image processing unit, a 16-bit personal computer as a controller, and an engineering workstation as a post processor. The dental cast is projected and scanned with a slit-ray laser beam.

Relationship between tumor (T) antigen expression and substituent effects on benzo [a] phenothiazines.

Human adenovirus, oncogene-type 12 infected HEp-2 cells were exposed to six benzo[a]phenothiazines. 5-Oxo-5H-benzo[a]phenothiazine (4) and 6-hydroxy-5-oxo-5H-benzo[a]phenothiazine (5) were moderately toxic. 9-Methyl-12H-benzo[a]phenothiazine (2), 10-methyl-12H-benzo[a]phenothiazine (3), 6-methyl-5-oxo-5H-benzo[a]phenothiazine (6), and 12H-benzo[a]phenothiazine (1) were not toxic in the system tested.

Diverse mutagenicity of methylbenz[c]acridines in the direct Ames' Salmonella mutagenicity assay.

The mutagenicity of eleven methylbenz[c]acridines (methyl-B[c]ACRs) was examined by the direct Ames' Salmonella mutagenicity assay on the standard tester strains of TA97a, TA98, TA100 and TA102, each of which is specific to a certain type of mutation. The Benz[c]acridines (B[c]ACRs) studied in this investigation were substituted with one to three methyl group(s) at the 5, 7, 8, 9, 10 and 11 position(s) of B[c]ACR. A certain degree of mutagenic activity was observed by all methyl-B[c]ACRs on at least one of the tester strains, indicating that even non-carcinogenic methyl-B[c]ACRs showed mutagenicity in the assay.

Correlations between topological resonance energy of methyl-substituted benz[c]acridines, benzo[a]phenothiazines and chrysenes, and their carcinogenic or antitumor activities.

In order to clarify the effects of methyl substitution on the carcinogenic activity, each resonance energy (RE) of benz[c]acridines, benzo[a]phenothiazines, chrysene, and their methyl derivatives was calculated by Aihara's TRE theory. Some correlations seem to exist between the values of resonance energy per pi-electron for the cationic species-with the lack of the atom having the highest approximate superdelocalizability (Sr'(E)) from their parents skeleton-and carcinogenic activity.

Synthesis and antitumor activity of 1-[2-(chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl- 1-urea s as potent anticancer agents.

10-[N-(Phthalimido)alkyl]-2-substituted-10H-phenothiazines and 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas were synthesized and found to have antiproliferative effects on human HEp-2 and L5178Y cell cultures. The multi-drug resistant subline of mouse lymphoma was sensitive to the reversal effects of some 10-[N-(phthalimido)alkyl]-2-substituted-10H-phenothiazines, while 1-(2-chloro-ethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1 -ureas were less effective but had a similar degree of antiproliferative effect on both cell lines.

Antitumor activity of phenothiazine-related compounds.

One of the biggest challenges in health care is the fight against tumors. Some phenothiazines have antitumor activity on HEp-2 tumor cells. In this study, we tested the antitumor effects of three series such as 10-nonsubstituted phenothiazines, 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines and 1-(chloroethyl)-3-(2-substituted-10H-phenothiazines-10-yl)alkyl-1-ureas with H, Cl and CF3 substitution at position C2.

Immunomodulating activities on cellular cytotoxicity and the blast transformation of human lymphocytes by 10-[n-(phthalimido)alkyl-2-substituted-10H-phenothiazines and 1-(2-chloroethyl)-3-(2-substituted-10 H-phenothiazin-10-yl)alkyl-1-ureas.

Phenothiazines, 10-[n-(phthalimido)alkyl-2-substituted-10H- phenothiazines, and 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas were investigated for their effects on antibody-dependent cellular cytotoxicity (ADCC), natural killer (NK) cells and the blast transformation of human peripheral blood mononuclear cells. All of the compounds dose-dependently suppressed mitogen-stimulated T cell proliferation. In contrast, a strong enhancing effect on NK cell activity was detected mostly in the case of 1-(2-choroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alk yl-1-ureas and their related compounds.

Relationship between resonance energy per pi-electron and carcinogenicity in arenes.

The resonance energy per pi-electron of various arenes was calculated using Aihara's TRE theory. There seemed to be a correlation between the resonance energy volume per pi-electron of the cation species (lacking a carbon atom) with the highest approximate superdelocalizability (Sr'(E)) from the parent skeleton and carcinogenicity, i.e.