scholarly journals In Vitro Antiherpesviral Activity of 5-Alkyl Derivatives of 1- -D-Arabinofuranosyluracil

1979 ◽  
Vol 16 (2) ◽  
pp. 158-163 ◽  
Author(s):  
H. Machida ◽  
S. Sakata ◽  
A. Kuninaka ◽  
H. Yoshino ◽  
C. Nakayama ◽  
...  
Keyword(s):  
Alkyl Derivatives ◽  
Derivatives Of

Synthesis and Cytostatic Activity of N-[2-(Phosphonomethoxy)alkyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds

2001 ◽  
Vol 66 (10) ◽  
pp. 1545-1592 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Votruba ◽  
Eva Tloušťová ◽  
Milena Masojídková
Keyword(s):  
Cytostatic Activity ◽  
Secondary Amines ◽  
Dimethylformamide Dimethylacetal ◽  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Related Compounds ◽  
Substituted Adenines

N6-Substituted adenine and 2,6-diaminopurine derivatives of 9-[2-(phosphonomethoxy)- ethyl] (PME), 9-[(R)-2-(phosphonomethoxy)propyl] [(R)-PMP] and enantiomeric (S)-PMP series were synthesized by reactions of primary or secondary amines with 6-chloro-9-{[2-(diisopropoxyphosphoryl)methoxy]alkyl}purines (26-28) or 2-amino-6-chloro-9-{[2-(diisopropoxy- phosphoryl)methoxy]alkyl}purines (29-31) followed by treatment of the diester intermediates32with bromo(trimethyl)silane and hydrolysis. Diesters32were also obtained by reaction ofN6-substituted purines with synthons23-25bearing diisopropoxyphosphoryl group. Alkylation of 2-amino-6-chloropurine (9) with diethyl [2-(2-chloroethoxy)ethyl]phosphonate (148) gave the diester149which was analogously converted toN6-substituted 2,6-diamino- 9-[2-(2-phosphonoethoxy)ethyl]purines151-153. Alkylation ofN6-substituted 2,6-diaminopurines with (R)-[(trityloxy)methyl]oxirane (155) followed by reaction of thus-obtained intermediates156with dimethylformamide dimethylacetal and condensation with diisopropyl [(tosyloxy)methyl]phosphonate (158) followed by deprotection of the intermediates159gaveN6-substituted 2,6-diamino-9-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]purines160-163. The highest cytostatic activityin vitrowas exhibited by the followingN6-derivatives of 2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (PMEDAP): 2,2,2-trifluoroethyl (53), allyl (54), [(2-dimethylamino)ethyl] (68), cyclopropyl (75) and dimethyl (91). In CCRF-CEM cells, the cyclopropyl derivative75is deaminated to the guanine derivative PMEG (3) which is then converted to its diphosphate.

Small 9-Alkyl Derivatives of 10-Hydroxycamptothecin with Potent Antitumor Activity in Vitro and in Vivo

2005 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
H. Gao ◽  
M. Huang ◽  
J. Sun ◽  
H. Shen ◽  
W. Lu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Alkyl Derivatives ◽  
Derivatives Of

A STUDY ON THE "IN VITRO" SYNTHESIS OF CITRULLINE: PART I. EFFECT OF SOME N-ALKYL DERIVATIVES OF ASPARTIG ACID

1964 ◽  
Vol 42 (9) ◽  
pp. 1317-1324 ◽  
Author(s):  
Louis Berlinguet ◽  
René Charbonneau
Keyword(s):  
Aspartic Acid ◽  
Inhibitory Action ◽  
Liver Homogenate ◽  
Chelating Agent ◽  
Magnesium Ion ◽  
Carbamyl Phosphate ◽  
In Vitro Synthesis ◽  
Alkyl Derivatives ◽  
Derivatives Of

The effects of various N-alkyl derivatives of aspartic acid on the synthesis of citrulline in the presence of a particulate fraction obtained from a rat liver homogenate were studied. Even though aspartic acid has no role in this synthesis, both N-methyl and N-isopropyl aspartic acids were found to increase the synthesis of citrulline by 60%, whereas N-cyclohexyl aspartic acid decreased it by 50%. N-Allyl aspartic acid has the strongest effect which is an almost complete inhibition at low concentration of 1.2 × 10−2 M.It seems that N-allyl aspartic acid inhibits directly or indirectly the first step in the synthesis of citrulline leading to the formation of carbamyl phosphate. At various concentrations, none of the intermediates in this synthesis, except magnesium ion, can reverse the inhibition. In order that N-allyl aspartic acid retain its inhibitory action, the ω-carboxyl group has to be free and the double bond in the allyl group must be intact. From these results, it is postulated that N-allyl aspartic acid acts as a chelating agent for magnesium.

Alkyl Hydrogen Phosphonate Derivatives of the anti-HIV Agent AZT may be Less Toxic than the Parent Nucleoside Analogue

1994 ◽  
Vol 5 (4) ◽  
pp. 271-277 ◽  
Author(s):  
C. McGuigan ◽  
P. Bellevergue ◽  
B. C. N. M. Jones ◽  
N. Mahmood ◽  
A. J. Hay ◽  
...  
Keyword(s):  
Nucleoside Analogue ◽  
Parent Drug ◽  
Antiviral Action ◽  
Alkyl Derivatives ◽  
Free Nucleotides ◽  
A Cell ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Long Chain

Novel alkyl hydrogen phosphonate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridite chemistry. These materials are designed to act as labile membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation has revealed the compounds to have a pronounced and selective antiviral action. Short-chain (C1-C7) alkyl derivatives are more potent than the parent hydrogen phosphonate, whilst one long-chain (C18) compound is less active. In an assay that demonstrates the toxicity of the parent drug AZT, the alkyl H-phosphonates appear to be less cytotoxic, whilst retaining full antiviral activity. Lastly, the compounds are all poorly active in a cell line (JM) that is poorly responsive to AZT, indicating that they act as depot forms of the nucleoside rather than of the free nucleotide.

Cytotoxic and non-cytotoxic N-alkyl derivatives of putrescine: effect on polyamine uptake and growth of prostatic cancer cells in vitro

1987 ◽  
Vol 36 (11) ◽  
pp. 1849-1852 ◽  
Author(s):  
Warren D.W. Heston ◽  
Kyoichi A. Watanabe ◽  
Krzysztof W. Pankiewicz ◽  
Douglas F. Covey
Keyword(s):  
Cancer Cells ◽  
Prostatic Cancer ◽  
Alkyl Derivatives ◽  
Polyamine Uptake ◽  
Derivatives Of

scholarly journals INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE

1953 ◽  
Vol 98 (3) ◽  
pp. 245-259 ◽  
Author(s):  
Igor Tamm ◽  
Karl Folkers ◽  
Clifford H. Shunk ◽  
Dorothea Heyl ◽  
Frank L. Horsfall
Keyword(s):  
Influenza Virus ◽  
Inhibitory Activity ◽  
Imidazole Ring ◽  
Virus Multiplication ◽  
Influenza B Virus ◽  
Influenza B ◽  
Active Compounds ◽  
Alkyl Derivatives ◽  
Derivatives Of

The degree of inhibition of multiplication of influenza B virus, Lee strain, in membrane cultures in vitro appears to be directly related to the concentration of the inhibitory compounds used in this investigation. With each of the alkyl derivatives of benzimidazole, evidence for such a relationship was obtained in the range between 60 and 90 per cent inhibition of virus multiplication. Alteration of the structure of benzimidazole by substitution of alkyl radicals at various positions in either the benzene or the imidazole ring resulted in diverse differences in the capacity to inhibit influenza virus multiplication in vitro. Minor increases in inhibitory activity resulted when one to three methyl groups were introduced at certain positions in the molecule. Marked increases in inhibitory activity were achieved by more extensive substitution in either the benzene or the imidazole ring. The position and nature of substituent groups appeared to be of decisive importance. Among the more highly active compounds were 2,4,5,6,7-pentamethyl-benzimidazole, 5,6-diethylbenzimidazole, and 2-ethyl-5-methylbenzimidazole. Further extension of the alkyl chain at position 2 caused no significant change in the inhibitory activity of the derivative. The most active compounds studied caused 75 per cent inhibition of Lee virus multiplication in membrane cultures in vitro at concentrations of approximately 0.0002 M. Some of the implications of these findings are discussed.

In vitro and in vivo evaluation of O-alkyl derivatives of tramadol

2008 ◽  
Vol 18 (5) ◽  
pp. 1674-1680 ◽  
Author(s):  
Liming Shao ◽  
Michael Hewitt ◽  
Thomas P. Jerussi ◽  
Frank Wu ◽  
Scott Malcolm ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
Alkyl Derivatives ◽  
Derivatives Of

Synthesis and Evaluation of Aromatic Surfactants as Potential Antibacterial and Cytotoxic Agents

2019 ◽  
Vol 16 (6) ◽  
pp. 478-484
Author(s):  
Kenia Barrantes ◽  
Mary Fuentes ◽  
Luz Chacón ◽  
Rosario Achí ◽  
Jorge Granados-Zuñiga ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Hela Cells ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Hydroxybenzoic Acid ◽  
Derivatives Of

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives

2019 ◽  
Vol 16 (12) ◽  
pp. 1360-1369 ◽  
Author(s):  
Rail Khaziev ◽  
Nikita Shtyrlin ◽  
Roman Pavelyev ◽  
Raushan Nigmatullin ◽  
Raylya Gabbasova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid Membranes ◽  
Specific Activity ◽  
Tuberculosis H37rv ◽  
Microbial Pathogens ◽  
Adamantane Derivatives ◽  
Carbon Cage ◽  
H37rv Strain ◽  
Derivatives Of

Background: Adamantane derivatives possess multiple pharmacological activities such as antiviral, anticancer, antimycobacterial, antidiabetic, antiparkinsonian and others. The interest of medicinal chemists in adamantane compounds is due to their unique spatial structure, high lipophilicity, and carbon cage rigidity. As a result, these molecules can easily penetrate biological lipid membranes and often have unique target-specific activity profile. Another pharmacophore studied in this work is pyridoxine (vitamin B6). Pyridoxine plays highly important roles in living cells as a key cofactor of many enzymes. On the other hand, its molecular scaffold is a valuable structural platform which has led to the development of several launched drugs (Pyritinol, Pirisudanol, Cycletanine, Mangafodipir) and a wide number of preclinical and clinical drug candidates. Objective: The objective of this study is a synthesis of pyridoxine-adamantane and pyridoxinecyclooctane dipharmacophore molecules. The underlying idea was to assess the antibacterial and antiviral potential of such dipharmacophores, based on multiple examples of promising antiinfective agents which have in their structures adamantane and pyridoxine moieties. Another specific reason was to explore the ability of pyridoxine pharmacophore to suppress the potential of microbial pathogens to develop resistance to drug molecules. Methods: In this study, a series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkyl amines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. All synthesized compounds have been tested for their in vitro activity against M. tuberculosis H37Rv strain and H3N2 (A/Aichi/2/68) influenza virus. Results: Series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkylamines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. Reaction of cycloalkylamines with pyridoxine derivatives, in which meta-hydroxyl and ortho-hydroxymethyl groups are protected by acetyl groups, represents a useful alternative to reductive amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza virus (EC50 52-88 µg/mL) that was comparable to the activity of Amantadine, though lower than the activity of Rimantadine. The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane. Conclusion: The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane.

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