Potential antidepressants: N-phenacyl derivatives of (E)-N-methyl-3-(6,11-dihydrodibenzo[b,e]thiepin-11-ylidene)propylamine

1988 ◽  
Vol 53 (4) ◽  
pp. 884-888 ◽  
Author(s):  
Zdeněk Polívka ◽  
Jiřina Metyšová ◽  
Martin Valchář ◽  
Miroslav Protiva
Keyword(s):  
Acute Toxicity ◽  
Potassium Carbonate ◽  
Induced Hypothermia ◽  
Activity Inhibition ◽  
The Common ◽  
Phenacyl Derivatives ◽  
Derivatives Of ◽  
Animal Tests

Reactions of (E)-N-methyl-3-(6,11-dihydrodibenzo[b,e]thiepin-11-ylidene)propylamine (V) with phenacyl chloride and 4-chlorophenacyl bromide in chloroform in the presence of sodium or potassium carbonate afforded the title compounds VI and VII. Their hydrochlorides showed very low acute toxicity in mice but in comparison with prothiadene (IV), they were less effective in the common animal tests used for assessing the thymoleptic activity (inhibition of reserpine-induced hypothermia and ptosis in mice, potentiation of yohimbine toxicity in mice, anticataleptic action in rats). These activity relations are in disagreement with those published for the analogous pair of 10,11-dihydrodibenz[b,f]azepine derivatives imipramine (I) and lofepramine (III).

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

1983 ◽  
Vol 48 (4) ◽  
pp. 1173-1186 ◽  
Author(s):  
Václav Bártl ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Marie Bartošová ◽  
Miroslav Protiva
Keyword(s):  
Acute Toxicity ◽  
Water Soluble ◽  
Hypotensive Activity ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Soluble Salts ◽  
Sleeping Time ◽  
Central Depression ◽  
Derivatives Of ◽  
Electroshock Seizures

Reactions of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins XIVa-XIVd with benzaldehyde, 3,4-dimethoxybenzaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 2-(2-dimethylaminoethoxy)benzaldehyde, 3-(2-dimethylaminoethoxy)benzaldehyde and 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde afforded a series of 19 hydrazones IIIa-Xc. Some of them showed the expected anticonvulsant effect but only towards pentetrazole; antagonism of maximal electroshock seizures was not observed. In general, the products have a character of tranquillizers: in higher does they produce central depression, potentiate the thiopental sleeping time, have hypothermic action; in single cases antiamphetamine, antireserpine, antihistamine and cataleptic effects were observed. The water-soluble salts of the basic hydrazones VIIIa, VIIIc, IXc and Xc, administered parenterally, showed a rather high acute toxicity and revealed also adrenolytic and hypotensive activity.

Acute Toxicity of Synthetic Pyrethroid Cypermethrin on the Common Carp (Cyprinus carpio L.) Embryos and Larvae

2005 ◽  
Vol 13 (5) ◽  
pp. 451-458 ◽  
Author(s):  
Rahmi Aydın ◽  
Kenan Köprücü ◽  
Mustafa Dörücü ◽  
Sibel Şimşek Köprücü ◽  
Murat Pala
Keyword(s):  
Acute Toxicity ◽  
Common Carp ◽  
Cyprinus Carpio ◽  
Synthetic Pyrethroid ◽  
Common Carp Cyprinus Carpio ◽  
Carp Cyprinus Carpio ◽  
The Common

scholarly journals Anthroponyms of Jewish Women in the 16th Century Grand Duchy of Lithuania

2012 ◽  
Vol 21 (26) ◽  
pp. 200-207
Author(s):  
Jūratė Čirūnaitė
Keyword(s):  
Average Length ◽  
Family Members ◽  
16Th Century ◽  
Canonical Forms ◽  
Family Status ◽  
Social Origin ◽  
Jewish Women ◽  
The Common ◽  
Grand Duchy Of Lithuania ◽  
Derivatives Of

The most popular names among Jewish women in 16th century Lithuania were Simcha, Marjam, Anna, Debora. The names were most frequently recorded as diminutives (63.3%), with only 36.4% appearing in canonical forms. The smallest group comprises names formed using only anthroponyms that were derived from those of (male) family members (29.6%). 35.2% of the namings are recorded as mixed type. The same number of women are recorded using only names in the documents.Personal names are included in 70.4% of recorded women’s namings. Andronyms (anthroponyms formed from the spouse’s name) were found in 64.8% of all the records. 9.3% of women’s namings include anthroponyms formed using the spouse’s patronymic. Only 1.9% of namings had a female patronymic (the derivative of the suffix -owna/-ewna).One-member female namings prevail (59.3%). Two-member namings comprise 33.3%. Three members are found in 5.6% of the namings, while four-membered ones comprise 1.9%. The average length of the namings is 1.5 times that of the anthroponyms.Common words explaining anthroponyms were found in 68.5% of the namings. Common words related to religion prevail (51.4%). 29.7% of the common words characterize relationships or family status, and only 10.8% describe occupation, post or trade (vocation). Common words describing descent (social origin) comprise only 8.1% of all the women’s namings.Namings consisting only of anthroponyms of family members can be subdivided into the following subgroups: 1) derivatives of the suffix -owaja/-ewaja; 2) derivatives of the suffix ‑owaja/-ewaja; 3) derivatives of the suffix -owaja/-ewaja + the genitive of a male patronymic; 4) derivatives of the suffix -owaja/-ewaja + a male patronymic + the genitive of a male patronymic. Namings without anthroponyms consisting of family members included names and names with common words. Mixed namings consisted of: 1) a name + a derivative of the suffix -owaja/-ewaja; 2) a derivative of the suffix -owaja/-ewaja + the genitive of a male patronymic + a name; 3) a derivative of the suffix -owaja/-ewaja + the genitive of a male patronymic + a name + a female patronymic.The most popular type of naming is a recorded name.

scholarly journals In Vitro Anti-Candida Activity and Action Mode of Benzoxazole Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5008
Author(s):  
Monika Staniszewska ◽  
Łukasz Kuryk ◽  
Aleksander Gryciuk ◽  
Joanna Kawalec ◽  
Marta Rogalska ◽  
...  
Keyword(s):  
Transport Process ◽  
Cross Resistance ◽  
Action Mechanism ◽  
Action Mode ◽  
Pleiotropic Action ◽  
Ergosterol Synthesis ◽  
Comparable Activity ◽  
Phenacyl Derivatives ◽  
Derivatives Of

A newly synthetized series of N-phenacyl derivatives of 2-mercaptobenzoxazole, including analogues of 5-bromo- and 5,7-dibromobenzoxazole, were screened against Candida strains and the action mechanism was evaluated. 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanone (5d), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichloro-phenyl)ethanone (5i), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,4,6-trichlorophenyl)ethanone (5k) and 2-[(5-bromo-1,3-benzoxazol-2-yl)sulfanyl]-1-phenylethanone (6a) showed anti-C. albicans SC5314 activity, where 5d displayed MICT = 16 µg/mL (%R = 100) and a weak anti-proliferative activity against the clinical strains: C. albicans resistant to azoles (Itr and Flu) and C. glabrata. Derivatives 5k and 6a displayed MICP = 16 µg/mL and %R = 64.2 ± 10.6, %R = 88.0 ± 9.7, respectively, against the C. albicans isolate. Derivative 5i was the most active against C. glabrata (%R = 53.0 ± 3.5 at 16 µg/mL). Benzoxazoles displayed no MIC against C. glabrata. Benzoxazoles showed a pleiotropic action mode: (1) the total sterols content was perturbed; (2) 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(3,4-dichlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichlorophenyl)ethanol (8h–i) at the lowest fungistatic conc. inhibited the efflux of the Rho123 tracker during the membrane transport process; (3) mitochondrial respiration was affected/inhibited by the benzoxazoles: 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-chlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanol 8c–d and 8i. Benzoxazoles showed comparable activity to commercially available azoles due to (1) the interaction with exogenous ergosterol, (2) endogenous ergosterol synthesis blocking as well as (3) membrane permeabilizing properties typical of AmB. Benzoxazoles display a broad spectrum of anti-Candida activity and action mode towards the membrane without cross-resistance with AmB; furthermore, they are safe to mammals.

Molecular Aspects of Herbicide Action on Protoporphyrinogen Oxidase

1993 ◽  
Vol 48 (3-4) ◽  
pp. 326-333 ◽  
Author(s):  
Beate Nicolaus ◽  
Gerhard Sandmann ◽  
Peter Böger
Keyword(s):  
Diphenyl Ether ◽  
Protoporphyrin Ix ◽  
Protoporphyrinogen Oxidase ◽  
Relative Specificity ◽  
Oxidase Inhibition ◽  
Dilution Experiments ◽  
Membrane Bound ◽  
The Common ◽  
Molecular Aspects ◽  
Derivatives Of

Abstract Protoporphyrinogen oxidase, the last enzyme of the common tetrapyrrole biosynthetic pathway, is inhibited by several peroxidizing compounds resulting in accumulation of photodynamic tetrapyrroles, mainly protoporphyrin IX. The inhibition characteristics of two chemi­cally unrelated compounds were studied using membrane bound protoporphyrinogen oxidase from corn etioplasts. As shown by Lineweaver-Burk-analysis, the inhibition of enzyme activity by the diphenyl ether oxyfluorfen and the cyclic imide MCI 15 are competitive with respect to the substrate. The competitive interaction of protoporphyrinogen and the two chemically un­related inhibitors indicate a relative specificity of the binding site. The reversibility of oxyfluorfen inhibition was evaluated by dilution experiments and was shown to be independent of the presence of DTT. The analysis of structure-activity-relationship on protoporphyrinogen oxidase inhibition was investigated with para-substituted derivatives of phenyl-3,4,5,6-tetrahydro-phthalimides. The results obtained by QSAR -calculation yielded a good correlation of the inhibitory activity determined by the lipophilicity of the para-substituent. These data point to one binding region of the inhibitors within a lipophilic environment associated with the active center of the enzyme.

scholarly journals Phenacylation of 6-Methyl-Beta-Nitropyridin-2-Ones and Further Heterocyclization of Products

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1682
Author(s):  
Eugene V. Babaev ◽  
Victor B. Rybakov
Keyword(s):  
Pyridinium Salt ◽  
Phenacyl Bromides ◽  
Acidic Conditions ◽  
Phenacyl Derivatives ◽  
Derivatives Of

Reaction between the derivatives of 6-methyl-beta-nitropyridin-2-one and phenacyl bromides was studied, and the yields observed were extremely low. The pyridones were converted via chloropyridines to methoxyderivatives, which were N-phenacylated. N-Phenacyl derivatives of 4,6-dimethyl-5-nitropyridin-2-one under the action of base gave 5-hydroxy-8-nitroindolizine and under acidic conditions gave 5-methyl-6-nitrooxazole[3,2-a]pyridinium salt, which underwent recycization with MeONa to 5-methoxy-8-nitroindolizine.

“Loop-at-a-Time” Design of Dynamic Surface Controllers for Nonlinear Systems

1998 ◽  
Vol 124 (1) ◽  
pp. 104-110 ◽  
Author(s):  
J. Christian Gerdes ◽  
J. Karl Hedrick
Keyword(s):  
Robust Control ◽  
Nonlinear Systems ◽  
Engine Speed ◽  
Design Procedure ◽  
Sequential Design ◽  
Bounded Region ◽  
Dynamic Surface ◽  
Mismatched Uncertainties ◽  
The Common ◽  
Derivatives Of

The use of multiple surface sliding controllers for robust control of nonlinear systems with mismatched uncertainties has produced a number of impressive applications, but also raised a few theoretical questions. Among the latter are the use of numerical differencing to obtain derivatives of desired trajectories, robustness to uncertainties in the gain terms and the common practice of filtering desired trajectories for implementation. This paper seeks to address these issues through the concept of a Dynamic Surface Controller, in which filters form an integral part of the structure. This filtering removes the need for numerical differencing and guarantees a certain smoothness, enabling other assumptions of smoothness to be relaxed. In this paper, the Dynamic Surface Controller is coupled with a sequential design procedure that carves a system workspace out of the state space. Within this bounded region, bounded tracking performance can be rigorously guaranteed in the presence of uncertainties and constraints such as rate limits and saturation can be systematically avoided. The design of a Dynamic Surface Controller and the advantages of the workspace concept are demonstrated in the context of engine speed control.

scholarly journals The reaction of iodobenzene-p-sulphonyl chloride (pipsyl chloride) with certain amino acids and peptides, and with insulin

1967 ◽  
Vol 102 (3) ◽  
pp. 815-824 ◽  
Author(s):  
J. C. Fletcher
Keyword(s):  
Amino Acids ◽  
Thin Layer ◽  
Acid Hydrolysis ◽  
Thin Layer Chromatography ◽  
Cysteic Acid ◽  
Buffer System ◽  
The Common ◽  
Layer Chromatography ◽  
Derivatives Of

1. A system of separation using buffered Celite columns is described that enables the pipsyl derivatives of most of the common amino acids to be separated. 2. The reaction of pipsyl chloride with several amino acids not included in previous studies has been investigated. In particular, knowledge of the acid-soluble pipsyl derivatives of arginine, histidine, lysine, tyrosine and cysteic acid has been extended. 3. Reproducible factors have been obtained that enable corrections to be applied for the breakdown of pipsylamino acids on acid hydrolysis. 4. The reaction of pipsyl chloride with peptides has been studied under various conditions. 5. The extent of the reaction between pipsyl chloride and insulin depends on the nature of the solvent-buffer system, and under the best conditions so far found is about 75% complete. 6. In an Appendix, the separation of pipsylamino acids by thin-layer chromatography is described.

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