scholarly journals The growth-inhibitory and carcinogenic properties of 4-aminostilbene and derivatives

1948 ◽  
Vol 241 (830) ◽  
pp. 147-195 ◽  
Keyword(s):  
Inhibitory Activity ◽  
Biological Activities ◽  
Essential Feature ◽  
Phenyl Group ◽  
Great Majority ◽  
Biological Properties ◽  
Hydrogen Atoms ◽  
Ethylene Bridge ◽  
Growth Inhibitory ◽  
Carcinogenic Action

Marked inhibition of the growth of the Walker rat carcinoma 256 is produced by administration of 4-aminostilbene and of 4-dimethylaminostilbene. From similar experiments with the Crocker sarcoma 180, the carcinoma C63, and spontaneous mammary cancer, it appears that the growth inhibitory action of these compounds is much less pronounced in mice. In a dosage of 200 to 250 mg. /kg. in the rat, both 4-amino- and 4-dimethylaminostilbene produce ( a ) gastro-intestinal submucous haemorrhage most evident in the pyloric portion of the stomach, ( b ) haematuria, and ( c ) haemolymph changes, while the former compound induces methaemoglobinaemia in addition. Using the Walker rat carcinoma 256 as the biological test object, a series of derivatives of 4-aminostilbene has been examined to determine the relationship between the growth-inhibitory effect and chemical constitution. The great majority of the active compounds can be defined as stilbenes with a basic substituent, the position of which is of paramount importance; thus o -dimethylaminostilbene is very much less active than the p -isomeride, and the m -compound is completely inactive. A further essential feature is the ethylene bridge, since activity disappears when either of its hydrogen atoms is substituted, when the bridge is reduced, when it is extended to contain three or four carbon atoms, or when either methine group is replaced by a nitrogen atom. Compounds in which the ethylene bridge is absent, or is replaced by oxygen or sulphur, are also inactive, and activity is further dependent upon the trans configuration of the molecule about the ethylenic bond, and to a large extent upon a free p' -position. These and other facts have suggested the working hypothesis that one of the features required for activity is an unbroken conjugation of the amino group with both nuclei, enabling the compound to assume some dipolar quinonoid character, which depends, among other things, on the co-planar arrangement of the two benzene nuclei which characterizes the trans form of the stilbenes. When evidence concerning steric conditions in the molecules (obtained mainly from the ultraviolet spectroscopy of 4-dimethylaminostilbene and thirteen of its alkyl derivatives) is compared with the biological activities of these compounds, a close parallel is suggested between lack of growth-inhibitory power and buckling of the molecule. Thus in the 4-dimethylaminostilbene derivatives with substituents on the x- and ?-carbon atoms of the ethylenic double bond, or with methyl groups at two ortho positions in a phenyl group, steric factors reduce the planarity of the molecule, thus affecting the conjugation resonance characteristic of the whole molecule. These compounds had previously been found to be non-inhibitory. All the evidence from diagrams, models and spectra suggests that steric interference with the planar configuration of molecules in this series varies continuously from the planar 4-dimethylaminostilbene to the highly buckled a/?-diethyl derivative. Inhibitory activity within this series appears to depend upon a conjunction of such factors as molecular size and shape, and the apposition of a planar molecule to a hypothetical adsorbing surface. In view of the previously suggested connexion between growth-inhibitory activity and tumour production, a number of selected aminostilbenes has been tested for carcinogenicity. Of seventy-two rats exposed to the action of 4-amino-, 4-acetamido-, 4-dimethylamino-, or 4-diethyIaminostilbene, twenty-three developed a total of eight sarcomata and thirty distant tumours mostly comprising squamous keratinizing carcinomata of the external acoustic duct, mammary adenomata, and cholangiomata. In a second series, the compounds 4-amino-, 4-dimethylamino- and 2,-methyl- 4-dimethylaminostilbene, and 1-(4'-dimethylaminophenyl)-2-(T-naphthyl)ethylene, were tested in male and female mice and rats. Of 120 rats exposed, forty-eight developed a total of twenty sarcomata at the site of injection and fifty-one tumours in organs distant from the site of injection, while of 120 mice similarly treated only four sarcomata and two distant tumours were recorded in five. The nature and distribution of the distant tumours induced in the rat strongly suggest some common feature in the carcinogenic action of aminostilbenes and 2-acetamidofluorene. Other points discussed include ( a ) the association between haemolymphatic changes and carcinogenesis, ( b ) the possible significance of the nitrogenous analogue 2-(4'-dimethylaminostyryl) quinoline in relation to the carcinogenic action of ‘styryl 430’, ( c ) a comparison of the biological properties of 4-dimethylaminostilbene and 4-dimethylaminoazobenzene, and ( d ) the dependence for manifestation of the growth-inhibiting action of the aminostilbenes upon a sufficiently low intake of dietary protein.

Nω-Hydroxy-L-arginine and Its Homologues. Chemical and Biological Properties. A Review

2004 ◽  
Vol 69 (3) ◽  
pp. 499-510 ◽  
Author(s):  
Petra Beranová ◽  
Karel Chalupský ◽  
Gustav Entlicher
Keyword(s):  
Inhibitory Activity ◽  
Biological Activities ◽  
Biological Effects ◽  
Biological Properties ◽  
No Synthase ◽  
Point Of View ◽  
No Donor ◽  
Good Substrate ◽  
No Formation ◽  
Vasorelaxant Activity

Nω-Hydroxy-L-arginine (NOHA) is a stable intermediate in NO formation from L-arginine catalyzed by NO synthase (NOS). Apparently, NOHA can be released and serve as a stable reserve NO donor (as a substrate of NOS) or transported and exert its own biological effects. It shows endothelium-dependent as well as endothelium-independent vasorelaxant activity. The latter case indicates that NOHA can be metabolized by pathways independent of NOS. These possibilities are discussed in detail. Of the available NOHA homologues homo-NOHA is a good substrate of NOS while nor-NOHA seems to be a very poor substrate of this enzyme. On the contrary, nor-NOHA exerts arginase inhibitory activity 20 times higher than NOHA whereas homo-NOHA is inactive. Detailed investigation of biological activities of NOHA and its homologues seems to be promising from the pharmacological point of view. A review with 43 references.

scholarly journals The inhibition of growth by chemical compounds

1942 ◽  
Vol 130 (860) ◽  
pp. 255-299 ◽  
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Usual Sense ◽  
Carcinogenic Activity ◽  
Related Substances ◽  
Inhibition Of Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Derivatives Of

In an extended investigation of the growth-inhibitory activity of carcinogenic compounds and related substances, over two hundred compounds were tested, including various 5-, 10- and 9 : 10-substituted benzanthracenes, dimethyl derivatives of anthracene, nitrogenous analogues of 1 : 2-benzanthracene, benzphenothiazines and dibenzphenothiazines, compounds related to 3 : 4-benzphenanthrene, dibenzfluorenes, dibenzcarbazoles, dibenzpyrenes, azonaphthalenes and related products, naphthylam ines and naphthaquinones, arsenonaphthalenes, derivatives of triphenylethylene, and diphenyl derivatives of indene, β -naphthindole and β -naphthofuran. A striking degree of correspondence was often shown by the inhibitory and carcinogenic activity of closely related com pounds (e. g. 5-alkyl benzanthracenes; dibenzfluorenes; dibenzphenanthrenes; 2 : 2'-azonaphthalene, 2 : 2'-diamino -1 : 1'-dinaphthyl and 3 : 4 : 5 : 6-dibenzcarbazole). However, no inhibitory activity was observed for certain carcinogenic 10- and 9 : 10- substituted benzanthracenes. On the other hand, inhibitory activity was noted in a few compounds (e. g. 1 : 2'-azonaphthalene) which have yielded few or no tum ours in exhaustive tests, and in some of a group of synthetic oestrogenic compounds which, although not carcinogenic in the usual sense, are nevertheless associated with the induction of individual types of tum our under special conditions. The relation between molecular structure and inhibitory activity depends in general upon an optimal degree of molecular complexity and upon certain more specific requirements. Nevertheless, the results obtained with derivatives of triphenylethylene suggest that inhibitory activity may still be shown by compounds diverging widely from the polycyclic structure and possessing only a skeletal resemblance. Diminution of inhibitory effect with increased substituent size was shown in the 5-alkyl benzanthracenes tested, although the same relation does not necessarily obtain for other positions. The influence of the nature of the substituent is seen (for example) in the contrast between 10-methyl-, 10-amino- and 10-cyano-l: 2-benzanthracene (inhibitory) and 10-isopropyl - 1:2-benzanthracene (inactive). Lastly, numerous experiments indicated that solubilization of an active compound usually entails decrease of activity, although certain apparent exceptions were encountered. In addition to the relationship between inhibitory activity and carcinogenicity, and that between both biological properties and chemical structure, consideration is also given to the mode of production of the inhibitory effect.

scholarly journals Synthesis and therapeutic potential of imidazole containing compounds

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ankit Siwach ◽  
Prabhakar Kumar Verma
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Properties ◽  
New Drugs ◽  
Hydrogen Atoms ◽  
Tautomeric Forms ◽  
Synthetic Routes ◽  
Derivatives Of ◽  
Heterocyclic Moiety ◽  
Antihistaminic Agent

Abstract Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857–1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.

scholarly journals Acetylcholine esterase inhibitory activity of green synthesized nanosilver by naphthopyrones isolated from marine-derived Aspergillus niger

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257071
Author(s):  
Ghada Mahmoud Abdelwahab ◽  
Amira Mira ◽  
Yuan-Bin Cheng ◽  
Tarek A. Abdelaziz ◽  
Mohamed Farid I. Lahloub ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Inhibitory Activity ◽  
Active Sites ◽  
Biological Activities ◽  
Biological Properties ◽  
Biological Evaluation ◽  
Acetylcholine Esterase ◽  
Protective Effects ◽  
Wide Range ◽  
First Time

Aspergillus niger metabolites exhibited a wide range of biological properties including antioxidant and neuro-protective effects and some physical properties as green synthesis of silver nanoparticles AgNP. The present study presents a novel evidence for the various biological activities of green synthesized AgNPs. For the first time, some isolated naphtho-γ-pyrones from marine-derived Aspergillus niger, flavasperone (1), rubrofusarin B (2), aurasperone A (3), fonsecinone A (4) in addition to one alkaloid aspernigrin A (7) were invistigated for their inhibitory activity of acetylcholine esterase AChE, a hallmark of Alzheimer’s disease (AD). The ability to synthesize AgNPs by compounds 3, 4 and 7 has been also tested for the first time. Green synthesized AgNPs were well-dispersed, and their size was ranging from 8–30 nm in diameter, their morphology was obviously spherical capped with the organic compounds. Further biological evaluation of their AChE inhibitory activity was compared to the parent compounds. AgNps dramatically increased the inhibitory activity of Compounds 4, 3 and 7 by 84, 16 and 13 fold, respectively to be more potent than galanthamine as a positive control with IC50 value of 1.43 compared to 0.089, 0.311 and 1.53 of AgNPs of Compounds 4, 3 and 7, respectively. Also compound 2 showed moderate inhibitory activity. This is could be probably explained by closer fitting to the active sites or the synergistic effect of the stabilized AgNPs by the organic compouds. These results, in addition to other intrinsic chemical and biological properties of naphtho-γ-pyrones, suggest that the latter could be further explored with a view towards other neuroprotective studies for alleviating AD.

scholarly journals Growth control in cultured 3T3 fibroblasts II. Molecular properties of a fraction enriched in growth inhibitory activity.

1982 ◽  
Vol 92 (2) ◽  
pp. 523-530 ◽  
Author(s):  
P A Steck ◽  
J Blenis ◽  
P G Voss ◽  
J L Wang
Keyword(s):  
Inhibitory Activity ◽  
Specific Activity ◽  
Biological Properties ◽  
Target Cells ◽  
3T3 Cells ◽  
Cultured Fibroblasts ◽  
Similar Treatment ◽  
Inhibition Of Growth ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Treatment of sparse, proliferating cultures of 3T3 cells with medium conditioned by exposure to density-inhibited 3T3 cultures resulted in an inhibition of growth and division in the target cells when compared to similar treatment with unconditioned medium. This growth inhibitory activity was fractionated by ammonium sulfate precipitation and gel filtration, yielding one fraction that was 35-fold enriched in specific activity. Analysis of the chemical and biological properties of this highly active fraction indicated that: (a) it is an endogenous cell product, synthesized by the 3T3 cells and shed into the medium; (b) it is a protein and its activity is sensitive to treatment with pronase; (c) the constituent polypeptide chains have molecular weights of 10,000 and 13,000; and (d) it is not cytotoxic and its effect on target cells are reversible. These results suggest that we have partially purified from conditioned medium an endogenous growth regulatory factor that may play a role in density-dependent inhibition of growth in cultured fibroblasts. We propose the term Fibroblast Growth Regulator to describe this class of molecules.

Design, Synthesis and Biological Evaluation of of Novel Anticancer Agent tert-butyl 1-phenyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

2013 ◽  
Vol 781-784 ◽  
pp. 2211-2214
Author(s):  
Biao Shi ◽  
Yi Qian Wang ◽  
Yao Yang ◽  
Peng Yu ◽  
Kui Lu
Keyword(s):  
Biological Activities ◽  
Biological Properties ◽  
Biological Evaluation ◽  
Nmr Spectrum ◽  
Design Synthesis ◽  
H Nmr ◽  
Growth Inhibitory ◽  
Wide Range ◽  
New Compounds ◽  
Synthesis And Biological Evaluation

Indole and its derivatives extensively exist in nature, which showed a wide range of biological activities. Recently, there is a growing tendency to develop some new methods for the synthesis of novel indole derivatives and to study their biological properties. In this paper, we would like to report the design, synthesis and biological evaluation of a novel series of tricyclic indoles by employing Pictet-Spengler reaction as key step. All the target compounds were synthesized in four steps in 68-78% overall yield, which were characterized by 1H-NMR spectrum. All this new compounds were tested in an MTT assay on HepG2 and K562 and HT-29. Two of them showed tumor cell growth inhibitory good activity.

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
Industrial Chemical ◽  
Anti Inflammatory ◽  
Pyridazinone Derivatives

A series of heterocyclic compounds incorporating pyridazine moiety were for diverse biological activities. Pyridazines and pyridazinones derivatives showed wide spectrum of biological activities such as vasodialator, cardiotonic, anticonvulsant, antihypertensive, antimicrobial, anti-inflammatory, analgesic, anti-feedant, herbicidal, and various other biological, agrochemical and industrial chemical activities. The results illustrated that the synthesized pyridazine/pyridazine compounds have diverse and significant biological activities. Mechanistic insights into the biological properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

The Molecular Diversity Scope of Urazole in the Synthesis of Organic Compounds

2019 ◽  
Vol 16 (7) ◽  
pp. 953-967 ◽  
Author(s):  
Ghodsi M. Ziarani ◽  
Fatemeh Mohajer ◽  
Razieh Moradi ◽  
Parisa Mofatehnia
Keyword(s):  
Biological Activities ◽  
Biological Properties ◽  
Biologically Active ◽  
Microtubule Assembly ◽  
Heterocyclic Molecules ◽  
Biological Perspective ◽  
Highly Active ◽  
Anti Inflammatory ◽  
High Yields ◽  
Short Time

Background: As a matter of fact, nitrogen as a hetero atom among other atoms has had an important role in active biological compounds. Since heterocyclic molecules with nitrogen are highly demanded due to biological properties, 4-phenylurazole as a compound containing nitrogen might be important in the multicomponent reaction used in agrochemicals, and pharmaceuticals. Considering the case of fused derivatives “pyrazolourazoles” which are highly applicable because of their application for analgesic, antibacterial, anti-inflammatory and antidiabetic activities as HSP-72 induction inhibitors (I and III) and novel microtubule assembly inhibitors. It should be mentioned that spiro-pyrazole also has biological activities like cytotoxic, antimicrobial, anticonvulsant, antifungal, anticancer, anti-inflammatory, and cardiotonic activities. Objective: Urazole has been used in many heterocyclic compounds which are valuable in organic syntheses. This review disclosed the advances in the use of urazole as the starting material in the synthesis of various biologically active molecules from 2006 to 2019. Conclusion: Compounds of urazole (1,2,4-triazolidine-3,5-dione) are the most important molecules which are highly active from the biological perspective in the pharmaceuticals as well as polymers. In summary, many protocols for preparations of the urazole derivatives from various substrates in multi-component reactions have been reported from different aromatic and aliphatic groups which have had carbonyl groups in their structures. It is noted that several catalysts have been synthesized to afford applicable molecules with urazole scaffolds. In some papers, being environmentally friendly, short time reactions and high yields are highlighted in the protocols. There is a room to synthesize new catalysts and perform new reactions by manipulating urazole to produce biologically active compounds, even producing chiral urazole component as many groups of chiral urazole compounds are important from biological perspective.

Synthesis and biological properties of cholecystokinin heptapeptide analogues containing D- and L-forms of tert-leucine or neopentylglycine in position 5

1991 ◽  
Vol 56 (10) ◽  
pp. 2209-2217 ◽  
Author(s):  
Jan Hlaváček ◽  
Jana Pírková ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Lenka Maletínská
Keyword(s):  
Gall Bladder ◽  
Solid Phase ◽  
Biological Activities ◽  
Biological Properties ◽  
Phase Synthesis ◽  
Structural Modifications ◽  
Bladder Contraction ◽  
Anorectic Effect ◽  
Carboxy Terminal ◽  
Anorectic Activity

Using solution or solid-phase synthesis we prepared the cholecystokinin fragment Boc-CCK-7 (Boc-Tyr-(SO3-.Na+)-Met-Gly-Trp-Met-Asp-PheNH2) and its four analogues in which the methionine moiety (Met) in the carboxy-terminal part is replaced by tert-leucine (Tle) or neopentylglycine (Neo) residue or D-enantiomers of these non-coded amino acids. These structural modifications led to reduction of the studied biological activities (gall bladder contraction, anorectic activity, analgetic and sedation activity) of all prepared analogues except Boc[Neo5]-CCK-7 which, being less analgetically active, retains full gall bladder and sedation activity of CCK-8. Moreover, its anorectic activity is substantially higher (400%). This analogue is very interesting particularly for its selectively increased (4x) anorectic effect compared with that of CCK-8.

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