Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine .beta.-hydroxylase

Padgette, Stephen R.; Herman, Heath H.; Han, Jin Hee; Pollock, Stanley H.; May, Sheldon W.

doi:10.1021/jm00376a024

Cited by 41 publications

(23 citation statements)

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“…administration. Padgette et al (1984) found a hypotensive effect of 4-S-CAP which reached a maximum of 25% at 1 h postinjection with a gradual return of the blood pressure to hypertensive levels after 3h.…”

Section: In Vivo Antimelanoma Effectmentioning

confidence: 85%

Phenolic Melanin Precursors Provide a Rational Approach to the Design of Antitumor Agents for Melanoma

Jimbow

Miura²,

Ito

et al. 1989

Pigment Cell Research

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A unique biological property of the melanocyte, melanin synthesis may permit a rational approach to design agents for better management of malignant melanoma. This in vivo and in vitro study examined the selective melanocytotoxicity and antimelanoma effects of phenolic compounds, cysteinylphenol (CP), cysteaminylphenol (CAP), and related compounds, and found (1) that both 4-S-CP and 4-S-CAP are melanin precursors, (2) that 4-S-CAP possesses a marked depigmenting potency with selective destruction of melanocytes in black follicles, and (3) a significant inhibition in the protein synthesis and tumor growth of B16 melanoma. Importantly, a whole body autoradiography indicated that these phenolic melanin precursors are selectively incorporated into melanoma tissues after i.p. administration.

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Section: In Vivo Antimelanoma Effectmentioning

confidence: 85%

Phenolic Melanin Precursors Provide a Rational Approach to the Design of Antitumor Agents for Melanoma

Jimbow

Miura²,

Ito

et al. 1989

Pigment Cell Research

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“…The pmethoxyphenethylamine hydrochloride and phenethylamine were obtained from Sigma, and the phenethylamine was crystallized as the hydrochloride salt by standard procedures . The /)-hydroxyphenyl-2-aminoethyl sulfide was prepared in our laboratory as described previously (Padgette et al ., 1984) . Percoll, penicillin/streptomycin/neomycin mixture (PSN; 5,000 U/ml of penicillin O, 5 mg/ml of streptomycin, 10 mg/ml of neomycin in 0.9% saline), gentamycin, glutamine, theophylline, unlabeled dopamine hydrochloride, unlabeled tyramine, and trypan blue were from Sigma.…”

Section: Methodsmentioning

confidence: 99%

Structural Requirements for Cocaine‐Sensitive and ‐Insensitive Uptake of Phenethylamines into the Adrenal Chromaffin Cell

Powers

Plaskon

Olsen

et al. 1995

Journal of Neurochemistry

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The adrenal medullary chromaffin cell is a commonly used model for the adrenergic neuron. Although much work has been done to study the transport system in the adrenal chromaffin vesicles, relatively little is known about cellular transport, especially with regard to structural features of phenethylamines required for intracellular accumulation. We have now investigated the structural requirements of phenethylamine‐related compounds for their accumulation into cultured adrenal chromaffin cells. We find that two types of cellular uptake, previously described only for dopamine, norepinephrine, and epinephrine, are also present for [3H]tyramine. Although two types of accumulation occur, tyramine accumulation occurs mainly via a cocaine‐insensitive process, whereas dopamine accumulation occurs predominantly via a cocaine‐sensitive process. The accumulation of [14C]‐phenethylamine and p‐methoxyphenethylamine is not affected by cocaine, suggesting that a ring hydroxyl substituent is necessary for cocaine‐sensitive accumulation. The compounds p‐hydroxyphenylpropylamine and p‐hydroxyphenyl‐2‐aminoethyl sulfide accumulate in the cell only via a cocaine‐insensitive process, indicating that lengthening of the aminoalkyl side chain prevents cocaine‐sensitive accumulation. We have performed conformational analyses of this series of compounds to determine whether the conformation of these compounds can be related to the kinetic data. For dopamine, tyramine, phenethylamine, and p‐methoxyphenethylamine, two groups of energy‐minimized conformers were found. We find that there is an approximately linear relationship between the Km values for these phenethylamines and the differences in minimized energies between the low‐ and highest energy conformer groups of each compound. A similar correlation was found for p‐hydroxyphenyl‐2‐aminoethyl sulfide. These results are consistent with the hypothesis that these compounds undergo a conformational change from the low‐energy conformer to the highest energy conformer before their cocaine‐insensitive accumulation.

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“…Chemicals L-dopa, L-ascorbic acid, Lcysteine, NP40, mushroom tyrosinase (4900 units/mg), and plasma MA0 (1000 units/g), were all obtained from Sigma Chemical Co. (St. Louis, MO). 4-S-CAP and a-Me-4-S-CAP were prepared by the methods of Padgette et al (1984). 4-S-HomoCAP was prepared by adapting our previous methods (Mura et al, 1987;Ito et al, 1981) used for the preparation of 4-S-CAP.…”

Section: Methodsmentioning

confidence: 99%

“…The oxidation of tyrosinase-specific substrates to produce cytotoxicity is the basis for the development of a chemotherapeutic agent against melanoma (Wick, 1980). However, in developing hypotensive agents, Padgette et al (1984) prepared 4-S-CAP and found it to be a good substrate for plasma MA0 as well. Kawase et al (1982) reported that various 3-substituted propylamines exerted cytotoxicity through the production of aldehydes by enzymic oxidative deamination using plasma amine oxidase.…”

Section: Introductionmentioning

confidence: 99%

4‐S‐Cysteaminylphenol and its Analogues as Substrates for Tyrosinase and Monoamine Oxidase

Pankovich

Jimbow

Ito

1990

Pigment Cell Research

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A phenolic amine compound, 4-S-cysteaminylphenol (4-S-CAP), was found to cause a selective destruction of follicular melanocytes. It was also recently found that 4-S-CAP can be a substrate for both tyrosinase and plasma monoamine oxidase (MAO). Both of these enzymes are capable of producing cytotoxic intermediates through their interaction with 4-S-CAP. To study the mechanism of selective melanocytotoxicity of phenolic amine compounds, we compared the in vivo depigmenting potency of 4-S-CAP and its three analogues; i.e., 4-S-HomoCAP, alpha-methyl(Me)-4-S-CAP and N,N-dimethyl(DiMe)-4-S-CAP, using black hair follicles. All four of these phenolic amine compounds possessed depigmenting potency. In this study we examined the kinetics of tyrosinase and MAO by these four compounds. 4-S-CAP and 4-S-HomoCAP were the substrates of both tyrosinase and MAO, whereas alpha-Me-4-S-CAP and N,N-DiMe-4-S-CAP were the substrates of tyrosinase alone. The rate of o-quinone formation by tyrosinase was not in parallel to the in vivo depigmenting potency of the tested compounds. It is therefore indicated that plasma MAO is not the enzyme directly responsible for the production of the melanocytotoxic intermediates from the phenolic amine compounds. We also found that the observed in vivo depigmentation results from complex processes involving the amount of o-quinone formed and the intracellular interaction of o-quinone with protein species.

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Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine .beta.-hydroxylase

Cited by 41 publications

References 0 publications

Phenolic Melanin Precursors Provide a Rational Approach to the Design of Antitumor Agents for Melanoma

Phenolic Melanin Precursors Provide a Rational Approach to the Design of Antitumor Agents for Melanoma

Structural Requirements for Cocaine‐Sensitive and ‐Insensitive Uptake of Phenethylamines into the Adrenal Chromaffin Cell

4‐S‐Cysteaminylphenol and its Analogues as Substrates for Tyrosinase and Monoamine Oxidase

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