Aminophenylacetic Acid Research Articles

Synergistic induction of cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid in combination with caffeine in human lymphocytes in vitro and in Ehrlich ascites tumour cells in vivo

We studied the effects of caffeine alone or in combination with homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE, NSC 290205) on the frequency of SCEs and lymphocyte proliferation kinetics. Caffeine was found to act synergistically with ASE on the induction of SCEs when the two components were administered in combination. Caffeine was also found to act synergistically with ASE in inducing cell-division delays. Enhanced cytogenetic damage by ASE was observed when Ehrlich ascites tumour cells (EAT cells) were exposed in vivo to caffeine. ASE alone or in combination with caffeine caused a dose-dependent increase in SCE rates and cell-division delays. SCEs were demonstrated in EAT-bearing mice, by the i.p. injection of BrdUrd adsorbed onto activated charcoal, 1 h after the i.p. injection of ASE and/or caffeine.

Effects of alkylating antineoplastics alone or in combination with 3‐aminobenzamide on genotoxicity, antitumor activity, and NAD levels in human lymphocytes in vitro and on ehrlich ascites tumor cells in vivo

Enhanced cytogenetic damage by the homo-aza-steroidal ester of p-bis(2-chloroethyl)-aminophenylacetic acid (ASE) was observed when human lymphocytes in vitro or Ehrlich ascites tumor (EAT) cells in vivo were exposed to nontoxic concentrations of 3-amino-benzamide (3-AB). 3-AB at these concentrations was found to enhance synergistically the cytogenetic damage induced in vivo by cyclophosphamide (CP), a metabolically activated chemotherapeutic, or chlorambucil (CBC) in EAT cells. One hour before i.p. injection of 5-bromodeoxyuridine (BrdUrd) adsorbed to activated charcoal, EAT-bearing mice treated i.p. with ASE or CP showed a dose-dependent increase in sister chromatid exchange (SCE) rates and cell division delays. The treatment of human lymphocytes in vitro with ASE led to the depletion of cellular NAD, and addition of 3-AB, a potent inhibitor of poly(ADP-ribose)polymerase [P(ADPR)polymerase], to ASE-treated human lymphocytes prevented the drop of NAD, which remained at approximately control levels. Also, the in vivo treatment of EAT cells with CBC, ASE, or CP led to the depletion of NAD, whereas addition of 3-AB to CBC-, ASE- or CP-treated cells prevented the drop of NAD, which remained at nearly control levels. 3-AB in conjunction with CBC, ASE, or CP increased the survival time of the EAT-bearing mice and markedly reduced the ascitic volume. Thus cytogenetic damage induced by ASE plus 3-AB in vitro and by CBC, ASE, or CP plus 3-AB in vivo correlates well with 1) the prevention of NAD depletion in the presence of 3-AB in cells treated with the same alkylating agents in vitro or in vivo and 2) the in vivo antitumor effect by ASE, CBC, or CP in combination with 3-AB.

Cell division delays and SCEs induced by modified steroidal derivatives of p-bis(2-chloro-ethyl)aminophenyl acetic acid in human lymphocytes

Cell division delays and SCEs induced by modified steroidal derivatives of p-bis(2-chloro-ethyl)aminophenyl acetic acid in human lymphocytes

Induction of cytogenetic damage by modified steroidal derivatives of p-bis(2-chloroethyl)aminophenylacetic acid in human lymphocytes

The effect of modified steroids, containing alkylating agents, on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenylacetic acid (ASE) was found to be the most effective in causing markedly increased SCE rates and cell division delays. The androsterone ester of p-bis(2-chloroethyl)aminophenylacetic acid (AE-CAPA) was found to be next in order of effectiveness with the lactone ester (LE-CAPA), chlorambucil ester 3β-hydroxy-13a-amino-13, 17-seco-5a-androstan-17-oic-13,17-lactam (CBC-HAAL) and chlorambucil (CBC) following. p-bis(2-chloroethyl)aminophenylacetic acid (CAPA) had only a small effect and 3β-hydroxy-13a-amino-13,17-seco-5a-androstan-17-oic-13,17-lactam (HAAL) had no effect at all. A correlation between potency for SCE induction, effectiveness in cell division delay and previously established antitumor activity of these drugs was observed.

Mutagenicity and clastogenicity of the antineoplastic agents homo-azasteroidal ester of p-bis(2-chloroethyl)aminophenyl acetic acid and chlorambucil

The mutagenic and clastogenic effects of the antineoplastic agents homo-aza-steroidal ester (ASE) and chlorambucil (CBC) were tested for their ability to induce mutations in the Salmonella/microsome system and SCE in CHO cells in culture. ASE was found to be positive in strains TA1535 and TA100 and in the newer strain TA102 with and without metabolic activation, while CBC caused histidine reversion in strain TA102 after the addition of mammalian liver microsomal extract (S9). In addition, both agents were found to be strongly positive for SCE induction. The mutagenic and clastogenic actions of both agents were of a dose-response type.

A novel synthesis of 3-cyanoindoles and a new route to indole-3-carboxylic acid derivatives

2-Alkyl-3-cyanoindoles are obtained when 1-alkylmethyl-2-chloro-(or 2-phenylsulfonyl)-3-phenylsulfonylindoles are reacted with excess azide ion (90°/DMF). The reaction is considered to occur by a fragmentation recombination process in which the Schiff's base 12 is of central importance. This proposal is supported by the formation of 2-substituted indole-3-carboxylates 17 from aldehydes and the α-phenylsulfonyl- o -aminophenylacetic acid ester derivative 16 .

Chromosomal aberration and SCE induction by the cytostatic factor homo-aza-steroidal ester of p-bis(2-chloroethyl)amino phenyl acetic acid on CHO cells in culture

Chromosomal aberration and SCE induction by the cytostatic factor homo-aza-steroidal ester of p-bis(2-chloroethyl)amino phenyl acetic acid on CHO cells in culture

Chromosome damage and SCE induced by the cytostatic factor homo-aza-steroidal ester of P-bis (2-chloro-ethyl) amino phenyl acetic acid in CHO cells in culture.

The cytogenetic effects of homo-aza-steroidal ester (ASE) on Chinese hamster ovary (CHO) cells in vitro are reported. It was found that treatment of cells with a dose as low as 0.025 micrograms/ml of ASE causes a significant number of abnormal metaphases containing mostly chromatid-type aberrations. Similarly, significant frequencies of SCE were induced with only 0.075 micrograms/ml of ASE.

Effects of homo-aza-steroidal ester of p-BIS(2-chloroethyl)amino phenyl acetic acid on lymphocytes stimulated with phytohemagglutinin in vitro

The effect of 2- bis(2-chloroethyl)amino phenyl acetic acid( I) of lactam( II) and of lactam ester( III) were tested in a 48 h culture of human lymphocytes from normal subjects. The experiments yielded evidence that (a) for compound I there is a concentration-dependent increase progressively in the cell damage from the lowest (0.128 × 10 −8 M/ml) the highest concentration used (0.384 × 10 −8 M/ml). On the whole, it was indicated that compound I was rendering the cells almost unable to divide and to incorporate [ 3H]-thymidine proportionally to the concentration used; (b) for compound II no cell damage was observed and its role remains obscure; (c) for compound III there was evidence that in a concentration of 1.42 sx 10 −9 M/ml (which is actually half the corresponding concentration of compound I) it exhibits inhibition of DNA synthesis and low number of mitosis as well as chromosome damage. A fact worth mentioning is that mitotic index and [ 3H]-thymidine incorporation showed the same pattern of response in the lymphocytes examined.

New spin-labeled biologically active compounds

1. The paramagnetic derivatives of diethylenimino-S-triazine, pentaethyleniminocyclotriphospha-zatriene, and p-N-di-(β-chloroethyl)aminophenylacetic acid were synthesized. 2. The 4-aminomethyl- and 4-(β-aminoethyl)-2, 2, 6,6-tetramethylpiperidine-1-oxyls were synthesized. 3. A study was made of the reaction of the new spin-labeled compounds with DNA, synthetic polynucleotides, and albumin. 4. A study was made of the τsec of the spin-labeled polynucleotides as a function of the action of deoxyribonuclease, temperature, and the formation of purine-pyrimidine complexes. 5. The paramagnetic ethers of cellulose were obtained by the condensation of alkali cellulose with the paramagnetic derivatives of dichloro- and diethyleniminotriazine, and also of pentaethyleniminocyclo-triphosphazatriene.

Inhibition of human platelet aggregation by a dibenzazepine compound (GP 44296) and by N-(2,6-dichlorophenyl)-o-aminophenylacetic acid (GP 45840).

Studies of the aggregation of human platelets indicate that compounds GP 44296 and GP 45840 inhibit the secondary phase of ADP-induced aggregation and collagen-induced aggregation; GP 44296 also inhibits the primary phase of ADP-induced aggregation. Our results suggest that these compounds are more active on platelet behavior in vitro than phenylbutazone, oxyphenbutazone, and sulfinpyrazone.

Synthesis ofα-aminophenylacetic acid

Synthesis ofα-aminophenylacetic acid

鎮痙作用を有するα-アミノフェニル酢酸誘導体およびその関連化合物の研究 (第1報)

鎮痙作用を有するα-アミノフェニル酢酸誘導体およびその関連化合物の研究 (第1報)

<I>Iso</I>amyl α- [N- (β-diethylaminoethyl)] -aminophenylacetate (Adopon) に閲する研究

1) The parenterally administered Adopon was observed to be distributed in the body rapidly. However, without being retained in various organs, it disappears rapidly. 2) Adopon incorporated into body was observed to be excreted in the urine only in a small amount. 3) Adopon may be split rapidly by the enzymes included in various organs. Isoamylalcohol was confirmed as a metabolite, therefore, α- [N- (β-diethylaminoethyl)] -aminophenyl acetic acid may also be considered to be produced. 4) Pharmacological activities of isoamylalcohol andα- [N- (β-diethylaminoethyl] -aminophenylacetic acid, which may be considered as the decomposed products of Adopon, were observed to be much weaker thanthat of Adopon. 5) Adopon-splitting esterase may be widely distributed among organs of various animals, especially rich in liver and little in intestine. 6) The reason why the action of Adopon in vivo is temporary or fluctuating may be due to the fact that this agents is rapidly split by this esterase.

Stereochemical studies. Part I. The relative configurations of (–)-aminophenylacetic acid (α-phenylglycine) and (–)-mandelic acid

Stereochemical studies. Part I. The relative configurations of (–)-aminophenylacetic acid (α-phenylglycine) and (–)-mandelic acid

鎭痙剤の研究 (第2報)

Monoalkylaminoethyl alcohol was prepared from monoalkylamine and ethylene oxide, derived to the chloride by the usual method, and reacted with α-aminophenylacetic acid esters or β-aminophenylethyl alcohol to obtain eight kinds of α-(N-sec-aminoethyl)-aminophenylacetic acid esters and eight kinds of β-(N-sec-aminoethyl)-aminophenylethyl alcohols.

Acetylation as a physiologic reaction.

After the ingestion of para-amino phenyl acetic acid by human beings it was found that this substance was detoxicated by acetylation of the amino group. When fed to rabbits, acetic acid was also employed as the detoxicating agent and p-acetyl aminophenyl acetic acid was excreted in the urine. When the p-amino phenyl-acetic acid was fed to dogs, however, the amino group remained free and the detoxication of the compound was accomplished by combining with glycocoll. Ortho, meta and para amino benzoic acids were ingested by human beings then fed to dogs and rabbits. All three compounds were excreted unchanged in the urine of the dog. The ortho amino benzoic was excreted unchanged by the human being and rabbit, but the meta and para amino benzoic were acetylated by the human being as well as by the rabbit. Ortho acetyl amino benzoic acid was prepared and fed to the dog and rabbit as well as taken by a human subject. The acetyl derivative was found to be non-toxic, and was in each case rapidly excreted unchanged. There was in no case a glycocoll compound formed as reported by Salkowski after feeding meta amino benzoic acid to a human being, dog and rabbit.