scholarly journals Development of new antibacterial agents

2017 ◽  
Vol 1 (2) ◽  
pp. 31-32
Author(s):  
Assia Keniche ◽  
Samia Bellifa ◽  
Hafida Hassaine ◽  
Joseph Kajima Mulengi
Keyword(s):  
Antibacterial Activities ◽  
Good Growth ◽  
Coupling Reactions ◽  
Ongoing Research ◽  
Available N ◽  
Synthetic Strategy ◽  
Clinical Complications ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Derivatives Of

Background: Antibiotics, as miraculous drugs, have been used extensively to confront fatal infection, even without prescriptions. However, the inappropriate and disproportionate use of antibiotics have led to the emergence of new drug-resistant bacteria1, which causes a high risk of serious diseases and dramatically aggravates the clinical complications in hospitals. Methods: By using the peptide coupling protocol, a simple straightforward synthesis of functionalized aziridines has been developed. By means of this synthetic strategy from readily available N-phtaloyl acide and 2-methylbenzosulfonate aziridine using DCC as coupling agent, new tosylates aziridines could be obtained. The coupling reactions occurred without a ring opening of the three membered ring. Results: This work describes new results of our ongoing research targeting new derivatives of biological interests. All the compounds were screened for their antibacterial activity; they all showed comparable moderate to good growth inhibitory activity with reference to tetracyclin and gentamicin. Conclusion: In conclusion, we reported the synthesis and a preliminary antibacterial evaluation of novel functionalized tosylaziridines. The synthetic strategy relies on the coupling reactions between tosylaziridines and amino acids. Moreover, and besides showing interesting antibacterial activities, the series of novel compounds can be further improved to serve as potential drug against nosocomial diseases.

Synthesis of New β-Lactam Analogs and Evaluation of Their Histone Deacetylase (HDAC) Activity

2007 ◽  
Vol 62 (11) ◽  
pp. 1459-1464 ◽  
Author(s):  
Seikwan Oh ◽  
Jae-Chul Jung ◽  
Mitchell A. Avery
Keyword(s):  
Histone Deacetylase ◽  
Hdac Inhibitors ◽  
Human Tumor ◽  
Coupling Reactions ◽  
Human Tumor Cell Lines ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Potent Growth ◽  
High Yields

A simple synthesis of the β -lactams 11 - 13 and 16 - 17 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involved the O-alkylation of 6-APA and the coupling reactions of freshly prepared N-carbobenzyloxy-L-prolines 5 and 6 and 6-aminopenicillanates 8 - 10 and 15 in high yields. It was found that all compounds show potent growth inhibitory activity on human tumor cell lines, the most potent compound 16 exhibiting an IC50 = 2.1 μM in vitro.

scholarly journals Design and Synthesis of Simplified Analogues of Pateamine A

2021 ◽  
Author(s):  
◽  
Hemi Cumming
Keyword(s):  
Genetic Diseases ◽  
Optimal Order ◽  
Coupling Reactions ◽  
Protein Targets ◽  
Design And Synthesis ◽  
Synthetic Strategy ◽  
Linear Sequence ◽  
Growth Inhibitory ◽  
Pateamine A

<p>Pateamine A (14) is a natural product that was extracted from a marine sponge off the coast of the South Island of New Zealand. It exhibits potent biological activity, mediated by a number of protein targets. The most sensitive of these towards pateamine are the eIF4A isoforms, which have roles in translation of RNA into proteins and in nonsensemediated decay. The inhibition of these enzymes may be beneficial in the treatment of cancer or certain types of genetic diseases. Unfortunately, the naturally available supply of pateamine is very limited and its total synthesis is complex. This provides an imperative for the design of a synthetic strategy that would allow the preparation of simplified analogues of pateamine to gain further insight into the necessary features for activity and selectivity of the eIF4A isoforms. Based on the principles of pharmacophore modification, chemical synthesis and the structure-activity relationships (SARs) reported by Romo and co-workers, a simplified analogue of pateamine, 107, was targeted that lacked a number of pendant methyl groups and contained a triazole in place of the thiazole. Synthesis of the target analogue 107 was achieved through preparation of four fragments, followed by an investigation of suitable coupling reactions and the optimal order of connectivity. This included the preparation of two macrocycles that lacked the trienecontaining sidechain, and of simplified model substrates that allowed investigation of two olefination reactions (namely, the Wittig and Julia-Kocienski reactions) for the attachment of the sidechain fragment. After substantial optimisation of the fragment preparation and connectivity, the complete synthesis of the target pateamine analogue 107 was achieved. The synthesis features: 1) a Julia Kocienski olefination between a highly functionalised three-carbon sulfone and a conjugated aldehyde to attach the sidechain; 2) copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction to form the triazole; 3) ring opening of a δ-substituted α,β-unsaturated lactone to access the Z,E-dienoate moiety; and 4) Yamaguchi macrolactonisation. This synthesis represents a convergent strategy with 11 steps in the longest linear sequence, which utilises easily accessible starting materials (i.e. furan (or cis-butenediol), epichlorohydrin, ε-caprolactone and 1,3-propanediol) and reagents. The approach is also broadly applicable to the preparation of a range of analogue variants. The simplified analogue (107) was found to have significantly lower activity, in comparison to pateamine A (14), in a growth inhibitory assay. Presuming this loss of bioactivity is at least partially caused by the incorporation of the triazole (in place of the thiazole), this raises an interesting question as to the role of the thiazole moiety in the bioactivity of pateamine A. The adaptation of the synthetic strategy devised in this thesis to the preparation of future analogues will enable study of the mechanism of action of pateamine and related compounds, and probe the requirements for effective binding to the eIF4A isoforms.</p>

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 In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pyloriInfection

2001 ◽  
Vol 45 (9) ◽  
pp. 2455-2459 ◽  
Author(s):  
Tsuneo Kanamaru ◽  
Yoshitaka Nakano ◽  
Yukio Toyoda ◽  
Ken-Ichiro Miyagawa ◽  
Mayumi Tada ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Anaerobic Bacteria ◽  
Antibacterial Activities ◽  
Mongolian Gerbils ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
H Pylori ◽  
Aerobic And Anaerobic

ABSTRACT The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 μg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure ofH. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

Total synthesis of novel dictyostatin analogs and hybrids as microtubule-stabilizing anticancer agents

2009 ◽  
Vol 81 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Ian Paterson ◽  
Nicola M. Gardner ◽  
Guy J. Naylor
Keyword(s):  
Total Synthesis ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Human Cancer Cell Lines ◽  
Synthetic Strategy ◽  
Sar Studies ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Microtubule Stabilizing Agent

Structural modification of the dictyostatin macrolide template through adaptation of our total synthesis has led to the identification of a number of potent analogs of this novel microtubule-stabilizing agent. A common synthetic strategy was exploited, employing a (Z)-selective Still-Gennari olefination between various advanced C11-C26 aldehyde and C4-C10 (or C1-C10) β-ketophosphonate intermediates. In vitro evaluation of the growth inhibitory activity of these analogs against both Taxol-sensitive and -resistant human cancer cell lines has provided a foundation for structure-activity relationship (SAR) studies to help define the pharmacophore region.

scholarly journals Tulasporins A–D, 19-Residue Peptaibols from the Mycoparasitic Fungus Sepedonium tulasneanum

2016 ◽  
Vol 11 (12) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Alexander Otto ◽  
Annegret Laub ◽  
Mark Haid ◽  
Andrea Porzel ◽  
Jürgen Schmidt ◽  
...  
Keyword(s):  
Phytopathogenic Fungi ◽  
Septoria Tritici ◽  
Good Growth ◽  
Significant Activity ◽  
H Nmr ◽  
Spectroscopic Analyses ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Mycoparasitic Fungus ◽  
Semi Solid

Four new 19-residue peptaibols, named tulasporins A–D (1–4), were isolated from the semi-solid cultures of Sepedonium tulasneanum. Their structures were elucidated on the basis of extensive ESI-HRMSn fragmentation studies as well as 1H NMR spectroscopic analyses. Interestingly, the structures of tulasporins A–D (1–4) resemble those of chrysospermins isolated earlier from cultures of S. chrysospermum. Previously, it was hypothesized that the peptaibol production by Sepedonium species correlates with the morphology of the aleurioconidia, as exclusively round-shaped aleurioconidia forming species produced peptaibols. Since the investigated Sepedonium tulasneanum produces oval aleurioconidia, this study can be considered as the first report of peptaibols from a Sepedonium strain with oval-shaped aleurioconidia. Thus, it could be demonstrated that both round as well as oval aleurioconidia forming Sepedonium species are able to produce peptaibols. Tulasporins A-D (1–4), when tested against phytopathogenic fungi, exhibited good growth inhibitory activity against both Botrytis cinerea and Phytophthora infestans, while they were devoid of significant activity against Septoria tritici.

Design, Synthesis, and Cancer Cell Growth Inhibitory Activity of Triphenylphosphonium Derivatives of the Triterpenoid Betulin

2017 ◽  
Vol 80 (8) ◽  
pp. 2232-2239 ◽  
Author(s):  
Olga V. Tsepaeva ◽  
Andrey V. Nemtarev ◽  
Timur I. Abdullin ◽  
Leysan R. Grigor’eva ◽  
Elena V. Kuznetsova ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
Cancer Cell Growth ◽  
Design Synthesis ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Derivatives Of

scholarly journals Design and Synthesis of Simplified Analogues of Pateamine A

2021 ◽  
Author(s):  
◽  
Hemi Cumming
Keyword(s):  
Genetic Diseases ◽  
Optimal Order ◽  
Coupling Reactions ◽  
Protein Targets ◽  
Design And Synthesis ◽  
Synthetic Strategy ◽  
Linear Sequence ◽  
Growth Inhibitory ◽  
Pateamine A

<p>Pateamine A (14) is a natural product that was extracted from a marine sponge off the coast of the South Island of New Zealand. It exhibits potent biological activity, mediated by a number of protein targets. The most sensitive of these towards pateamine are the eIF4A isoforms, which have roles in translation of RNA into proteins and in nonsensemediated decay. The inhibition of these enzymes may be beneficial in the treatment of cancer or certain types of genetic diseases. Unfortunately, the naturally available supply of pateamine is very limited and its total synthesis is complex. This provides an imperative for the design of a synthetic strategy that would allow the preparation of simplified analogues of pateamine to gain further insight into the necessary features for activity and selectivity of the eIF4A isoforms. Based on the principles of pharmacophore modification, chemical synthesis and the structure-activity relationships (SARs) reported by Romo and co-workers, a simplified analogue of pateamine, 107, was targeted that lacked a number of pendant methyl groups and contained a triazole in place of the thiazole. Synthesis of the target analogue 107 was achieved through preparation of four fragments, followed by an investigation of suitable coupling reactions and the optimal order of connectivity. This included the preparation of two macrocycles that lacked the trienecontaining sidechain, and of simplified model substrates that allowed investigation of two olefination reactions (namely, the Wittig and Julia-Kocienski reactions) for the attachment of the sidechain fragment. After substantial optimisation of the fragment preparation and connectivity, the complete synthesis of the target pateamine analogue 107 was achieved. The synthesis features: 1) a Julia Kocienski olefination between a highly functionalised three-carbon sulfone and a conjugated aldehyde to attach the sidechain; 2) copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction to form the triazole; 3) ring opening of a δ-substituted α,β-unsaturated lactone to access the Z,E-dienoate moiety; and 4) Yamaguchi macrolactonisation. This synthesis represents a convergent strategy with 11 steps in the longest linear sequence, which utilises easily accessible starting materials (i.e. furan (or cis-butenediol), epichlorohydrin, ε-caprolactone and 1,3-propanediol) and reagents. The approach is also broadly applicable to the preparation of a range of analogue variants. The simplified analogue (107) was found to have significantly lower activity, in comparison to pateamine A (14), in a growth inhibitory assay. Presuming this loss of bioactivity is at least partially caused by the incorporation of the triazole (in place of the thiazole), this raises an interesting question as to the role of the thiazole moiety in the bioactivity of pateamine A. The adaptation of the synthetic strategy devised in this thesis to the preparation of future analogues will enable study of the mechanism of action of pateamine and related compounds, and probe the requirements for effective binding to the eIF4A isoforms.</p>

Sign in / Sign up

Export Citation Format

Share Document