Papers by Dimitri komiotis
Purpose: We have previously shown that newly synthesized fluoro-glucopyranosyl derivatives of ket... more Purpose: We have previously shown that newly synthesized fluoro-glucopyranosyl derivatives of ketonucleosides represent a group of antiviral drugs potent against RNA viruses. The aim of the present study was to ascertain whether these compounds are equally efficient in combating DNA viruses in comparison with the commercially available drug ganciclovir. Methods: As a study model, the pseudorabies virus (NIA3 strain) and pig kidney cells (PK-15) were used. Results: Our results indicated that 1-(6-O-acetyl-3,4-dideoxy-3-fluoro-β-D-glycero-hex-3-enopyranosyl-2-ulose)-N4-benzoyl cytosine (compound 2) is a potent inhibitor of pseudorabies replication, with higher antiviral activity than was found for ganciclovir. Izvleček Namen: V predhodnih raziskavah smo dokazali, da so de novo sintetizirani derivati fluoro-glukopiranozil ketonukleotidov skupina obetajo~ih antivirusnih substanc proti RNA virusom. Zato je bil cilj tega dela preu~iti, ali so te substance prav tako u~inkovite v boju proti DNA virusom v primerjavi z komercialnim zdravilom Ganciclovir. Metode: Uporabili smo model Pseudorabies virusa (NIA3) in pra{i~je ledvi~ne epitelijske celice (celi~na linija PK-15). Rezultati: Rezultati so pokazali, da je 1-(6-O-acetil-3,4-dideoksi-3-fluoroβ-D-glicero-hex-3-enopiranozil-2uloza)-N4-benzoil citozin (substanca 2) mo~an inhibitor replikacije pseudorabies virusa z mo~nej{im u~inkom kot ga ima Ganciclovir.
Synlett, Jan 2, 2020
S. aureus str. Newman MIC = 27 µg/mL S. pneumoniae DSM20566 MIC = 9 µg/mL S. pneumoniae DSM11865 ... more S. aureus str. Newman MIC = 27 µg/mL S. pneumoniae DSM20566 MIC = 9 µg/mL S. pneumoniae DSM11865 MIC = 9 µg/mL and deprotection 17 new pentenomycin derivatives combined yield range for coupling and deprotection steps: 39-94%
Synthesis and structural characterization of neutral “3+2” oxorhenium and oxotechnetium complexes of the 2-mercaptoethyl-N-glycine (SNO)/2,2′-bipyridine (NN) mixed ligand system
Inorganica Chimica Acta, Aug 1, 2007
Neutral, hexacoordinated “3+2” mixed ligand oxorhenium (1) and oxotechnetium (2) complexes of the... more Neutral, hexacoordinated “3+2” mixed ligand oxorhenium (1) and oxotechnetium (2) complexes of the general formula MO[SNO][NN], where M=Re or 99Tc, SNO is 2-mercaptoethyl-N-glycine and NN is 2,2′-bipyridine (bpy), were synthesized by simultaneous action of the tridentate SNO and the bidentate NN ligand on ReOCl3(PPh3)2 or 99TcO-gluconate precursors in a 1:1:1 molar ratio. Both complexes were characterized by elemental analysis, IR
European journal of medicinal chemistry, Apr 1, 2011
The synthesis of pyrimidine unsaturated keto and exomethylene arabinopyranonucleoside analogs as ... more The synthesis of pyrimidine unsaturated keto and exomethylene arabinopyranonucleoside analogs as potential antitumor and antiviral agents is described. Commercially available 1,2,3,4-tetra-O-acetyl-D-arabinopyranose (1) was condensed with silylated thymine, uracil, 5-fluorouracil, N 4-benzoyl cytosine and 5-(trifluoromethyl)uracil, respectively, deacetylated and acetylated to afford 1-(3,4-O-isopropylidenea-D-arabinopyranosyl)pyrimidine analogs 4. Two different synthetic routes were investigated for the conversion of compounds 4 into the new 1-(2,3,4-trideoxy-2-methylene-a-pent-3-enopyranosyl)nucleoside derivatives of thymine (10a), uracil (10b), 5-fluorouracil (10c) and N 4-benzoyl cytosine (10d). Only the first approach could afford derivative 10d. Debenzoylation of 10d afforded 1-(2,3,4-trideoxy-2-methylenea-pent-3-enopyranosyl)cytosine (10f). The first approach resulted also to the 2-keto-3,4-unsaturated analogs 9. The new analogs did not show inhibition of DNA and RNA virus replication in cell culture. The 2 0-ketonucleoside derivatives 9 were found to be more cytostatic than the corresponding 2 0-exomethylene nucleosides 10. The 5-fluorouracil unsaturated keto derivative 9c and the exomethylene derivatives 10c and 13c showed antiproliferative activity in the lower micromolar range. Experimental evidence revealed that 9c, 10c and 13c may act as novel types of 5-fluorouracil releasing prodrugs, and points to thymidylate synthase as target for their cytostatic action.
Bioorganic Chemistry, Dec 1, 2010
The 3-deoxy-3-fluoro-6-S-(2-S-pyridyl)-6-thio-b-D-glucopyranosyl nucleoside analogs 7 were prepar... more The 3-deoxy-3-fluoro-6-S-(2-S-pyridyl)-6-thio-b-D-glucopyranosyl nucleoside analogs 7 were prepared via two facile synthetic routes. Their precursors, 3-fluoro-6-thio-glucopyranosyl nucleosides 5a-e, were obtained by the sequence of deacetylation of 3-deoxy-3-fluoro-b-D-glucopyranosyl nucleosides 2a-e, selective tosylation of the primary OH of 3 and finally treatment with potassium thioacetate. The desired thiolpyridine protected analogs 7a-c,f,g were obtained by the sequence of deacetylation of 5a-c followed by thiopyridinylation and/or condensation of the corresponding heterocyclic bases with the newly synthesized peracetylated 6-S-(2-S-pyridyl) sugar precursor 13, which was obtained via a novel synthetic route from glycosyl donor 12. None of the compounds 6 and 7 showed antiviral activity, but the 5-fluorouracil derivative 7c and particularly the uracil derivative 7b were endowed with an interesting and selective cytostatic action against a variety of murine and human tumor cell cultures.
A Facile, One‐Step Conversion of 6‐O‐Trityl and 6‐O‐TBDMS Monosaccharides into the Corresponding Formate Esters
Journal of Carbohydrate Chemistry, Aug 1, 2006
... Dimitri Komiotis a * , George Agelis a , Stella Manta a , Niki Tzioumaki a , Evangelia Tsouka... more ... Dimitri Komiotis a * , George Agelis a , Stella Manta a , Niki Tzioumaki a , Evangelia Tsoukala a & Kostas Antonakis b pages 441-450. ... 769–780. [CrossRef], [Web of Science ®] View all references 22. Franke, F. and Guthrie, RD 1977. Tert‐butyldimethylsilyl ethers of sucrose. ...
in Vivo, Feb 27, 2018
Background/Aim: The aim of the present study was to investigate the antioxidant effects of a feed... more Background/Aim: The aim of the present study was to investigate the antioxidant effects of a feed supplemented with polyphenolic additives from olive mill wastewater (OMW) on lambs. Materials and Methods: Lambs received breast milk until the postnatal period, and then they were divided into two groups and received control and OMW feed for 55 days. Redox biomarkers were measured in blood and tissues at days 15, 42 and 70 after feeding. Results: Feed supplemented with OMW reduced thiobarbituric acid reactive species and protein carbonyls and increased total antioxidant capacity, glutathione and catalase activity in both blood and tissues. Conclusion: The administration of OMW-containing feed reinforced the antioxidant defense of lambs, which may improve their wellbeing and productivity. Additionally, this exploitation of OMW may solve problems of environmental pollution in areas with olive oil industries. Mediterranean countries are responsible for 95% of worldwide olive oil production (1). In Greece, the extraction and manufacture of olive oil is carried out in about 2,400 small scale agro-industrial units scattered throughout the country. These processes produce two waste streams: olive mill residual solids and olive mill wastewaters (OMW). OMW are formed from the water content of the fruit itself and the water used to wash and process them, and amounts to 0.5-3.25 m 3 per 1,000 kg of olives (2). Typically, the composition of OMW is water, organics and mineral salts. OMW comprises large amounts of organic (e.g. fats, lipids, polyphenols), inorganic constituents and water; a part of the organic fraction is composed of phenols (1). These compounds are responsible for its black color, toxicity, phytotoxicity and antibacterial properties (3). It is estimated that around 30 million cubic meters of OMW are generated annually in the Mediterranean area (4). Disposal of OMW causes serious environmental problems, such as soil contamination, water body pollution, underground seepage and odor (5). The environmental problems and potential hazards caused by OMW have prompted many countries to limit its discharge. Varied new technologies for reducing its pollutant power (e.g. physicochemical and biological methods), have been investigated in recent years (1). Technologies such as advanced oxidative processes have been proposed, but these are characterized by high operational costs and frequently require complex maintenance and availability of experienced personnel (6). Thus, an environmentally safe and costeffective treatment of OMW has not yet been found (7). Oleuropein, tyrosol and hydroxytyrosol are the main phenolic compounds found in OMW. Other phenolic compounds that are found in olive oil are caffeic acid, vanillic acid, coumaric acid, ferulic acid, gallic acid, hydroxybenzoic acid, kaempherol, apigenin and quercetin (8, 9). Despite toxic effects exhibited at high concentrations, these polyphenols also exhibit antioxidant activity. Therefore, the polyphenolic content of OMW could represent a source of antioxidants in different fields, such as nutrition, 291 This article is freely accessible online.
Bioorganic Chemistry, Apr 1, 2010
The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-b-D-glucopyranosyl nucleosides of 5-... more The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-b-D-glucopyranosyl nucleosides of 5-fluorouracil (6a), N 6-benzoyl adenine (6b), uracil (6c), thymine (6d) and N 4-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regioselective 2 0-O-deacylation afforded the partially acetylated dideoxynucleoside analogues of 5-fluorouracil (5a) and N 6-benzoyl adenine (5b), respectively. Direct oxidation of the free hydroxyl group at the 2 0-position of 5a,b, with simultaneous elimination reaction of the b-acetoxyl group, afforded the desired unsaturated 4,6-dideoxy-3-fluoro-2-keto-b-D-glucopyranosyl derivatives 6a,b. Compounds 1c-e were used as starting materials for the synthesis of the dideoxy unsaturated carbonyl nucleosides of uracil (6c), thymine (6d) and N 4-benzoyl cytosine (6e). Similarly a protection-selective deprotection sequence followed by oxidation of the free hydroxyl group at the 2 0-position of the dideoxy benzoylated analogues 9c-e with simultaneous elimination reaction of the b-benzoyl group, gave the desired nucleosides 6c-e. None of the compounds was inhibitory to a broad spectrum of DNA and RNA viruses at subtoxic concentrations. The 5-fluorouracil derivative 6a was more cytostatic (50% inhibitory concentration ranging between 0.2 and 12 lM) than the other compounds.
International Journal of Molecular Sciences, Jul 20, 2007
Fluorinated nucleoside analogues are known as antitumor, antiviral and chemotherapeutic agents, a... more Fluorinated nucleoside analogues are known as antitumor, antiviral and chemotherapeutic agents, although the antioxidant activity of this kind of molecules is not yet investigated. In this study we have tested the antioxidant activity of a series of modified pyrano-nucleoside analogues using three in vitro assays. Firstly, the antioxidant capacity of the products was assessed using the DPPH assay and secondly, in order to examine the ability of the products to protect DNA from the activity of reactive oxygen species (ROS), a peroxyl radical (ROO •) and a hydroxyl radical (OH •) induced DNA strand scission assay were used. None of the molecules showed the ability to scavenge DPPH radical and prevent OH • induced DNA strand breakage. Although, most of the tested nucleoside analogues, had the ability to prevent ROO • induced DNA damage.
European journal of medicinal chemistry, Feb 1, 2008
The protected b-nucleosides 1-(2,4,6-triO -acetyl-3-deoxy-3-fluoro-b-D-glucopyranosyl)-N 4-benzoy... more The protected b-nucleosides 1-(2,4,6-triO -acetyl-3-deoxy-3-fluoro-b-D-glucopyranosyl)-N 4-benzoyl cytosine (2a) and 9-(2,4,6-triO -acetyl-3-deoxy-3-fluoro-b-D-glucopyranosyl)-N 6-benzoyl adenine (2b), were synthesized by the coupling of peracetylated 3-deoxy-3-fluoro-D-glucopyranose (1) with silylated N 4-benzoyl cytosine and N 6-benzoyl adenine, respectively. The nucleosides were deacetylated and several subsequent protection and deprotection steps afforded the partially acetylated nucleosides of cytosine 7a and adenine 7b, respectively. Finally, direct oxidation of the free hydroxyl group at 4 0-position of 7a and 7b, and simultaneous elimination reaction of the b-acetoxyl group, afforded the desired unsaturated 3-fluoro-4-keto-b-D-glucopyranosyl derivatives. These newly synthesized compounds were evaluated for their potential antitumor and antiviral activities. Compared to 5FU, the newly synthesized derivatives showed to be more efficient as antitumor growth inhibitors and they exhibited direct antiviral effect toward rotavirus.
Carbohydrate Research, Sep 1, 2011
European journal of medicinal chemistry, Nov 1, 2011
This report describes the total and facile synthesis of 3 0-C-cyano & 3 0-C-cyano-3 0-deoxy pyrim... more This report describes the total and facile synthesis of 3 0-C-cyano & 3 0-C-cyano-3 0-deoxy pyrimidine pyranonucleosides. Reaction of 3-keto glucoside 1 with sodium cyanide gave the desired precursor 3-C-cyano-1,2:5,6-di-O-isopropylidene-aD -glucofuranose (2). Hydrolysis followed by acetylation led to the 1,2,3,4,6-penta-O-acetyl-3-C-cyano-D-glucopyranose (4). Compound 4 was condensed with silylated 5-fluorouracil, uracil, thymine and N 4-benzoylcytosine, respectively and deacetylated to afford the target 1-(3 0-C-cyano-b-D-glucopyranosyl)nucleosides 6aed. Routine deoxygenation at position 3 0 of cyanohydrin 2, followed by hydrolysis and acetylation led to the 3-C-cyano-3-deoxy-1,2,4,6-tetra-O-acetyl-D-allopyranose (10). Coupling of sugar 10 with silylated pyrimidines and subsequent deacetylation yielded the target 1-(3 0-C-cyano-3 0-deoxy-b-D-allopyranosyl)nucleosides 12aed. The new analogues were evaluated for their antiviral and cytostatic activities. It was found that 6a was endowed with a pronounced anti-proliferative activity that was only 2-to 8-fold less potent than that shown for the parental base 5-fluorouracil. None of the compounds showed activity against a broad panel of DNA and RNA viruses.
ChemInform, Feb 19, 2013
Stereocontrolled Facile Synthesis and Biological Evaluation of (3'S) and (3'R)-3'-Amino (and Azid... more Stereocontrolled Facile Synthesis and Biological Evaluation of (3'S) and (3'R)-3'-Amino (and Azido)-3'-deoxy Pyranonucleosides.-A variety of 3'-amino-3'-deoxypyranonucleosides and their 3'-azide precursors are designed, synthesized and evaluated for their biological activities. None of the products show any antiviral activity such as (VIII). However, 5-fluorouracil derivatives such as (VIII) are found to be moderately cytostatic against L1210 and Hela cells.-(MANTA, S.;
Nucleosides, Nucleotides & Nucleic Acids, Jul 1, 2012
Chemischer Informationsdienst, Jun 10, 1986
ChemInform Abstract: Synthesis of 7-[3-Bromo-3,4-dideoxy-6-O-(2-hydroxyethyl)-β-D-glycero- hex-3-enopyranosyl-2-ulose]theophylline
Chemischer Informationsdienst, Jul 1, 1986
Wie im Formelschema skizziert, wird das im Titel genannte ungesattigte Bromnucleosid (VIb), das n... more Wie im Formelschema skizziert, wird das im Titel genannte ungesattigte Bromnucleosid (VIb), das nach Kupplung an ungesattigte Fettsauren auf seine Cytotoxizitat gepruft werden soll, synthetisiert.
Medicinal Chemistry, Apr 17, 2020
Medicinal Chemistry, Jul 24, 2015
Undoubtedly, efficient cancer treatment is a significant challenge for the scientific community t... more Undoubtedly, efficient cancer treatment is a significant challenge for the scientific community the last decades. Despite tremendous progress made towards this direction, there are still efforts needed to discover new anticancer drugs. In this work, a series of N-substituted pyrrole-based scaffolds have been synthesized and evaluated for antiproliferative activity against a panel of cancer cell lines (L1210, CEM and HeLa). Furthermore, in order to discover new scaffolds as antivirus agents all the examined compounds were evaluated for antivirus activity against different types of DNA and RNA viruses. The key feature of the above structures is the existence of an aromatic ring with at least one hydrogenbonding donor and acceptor group. Results have shown interesting cytostatic activity for three of the synthesized compounds (1, 3 and 9). Especially, compound 1, containing a tropolone ring, proved to be the most promising scaffold (IC 50 :10-14 μΜ) for the development of novel potential anticancer agents. In addition, compound 1 has shown interesting antivirus activity as a scaffold against a variety of viruses.
Journal of Agricultural and Food Chemistry, Jul 16, 2008
Recently, phytochemical compounds present in legumes have gained a lot of interest because they a... more Recently, phytochemical compounds present in legumes have gained a lot of interest because they are considered to be possible chemopreventive agents. In the present study, 14 polyphenolic compounds were extracted and identified from two unique varieties of Leguminosae family plants cultivated in Greece and screened for their antioxidant and chemopreventive properties. Ten polyphenolic fractions, which are mainly mixtures of two compounds and five pure flavonoids, were isolated from the methanolic extracts of aerial plant parts of Vicia faba and Lotus edulis (Leguminosae), respectively. All of these fractions exhibited significant DPPH • radical scavenging capacity. Furthermore, they exerted significant protective activity against free radical-induced DNA damage. This activity was more potent against ROO • radical-induced DNA damage than against that induced by OH • radicals. Finally, they exhibited significant ability to inhibit the activity of the topoisomerase I enzyme. These results imply that the polyphenolic compounds identified in the fractions were responsible of the observed properties of the fractions and the initial extracts and indicate different mechanisms by which these phenolic compounds may act as chemopreventive agents.
Carbohydrate Research, Feb 1, 2011
A novel series of exomethylene-and keto-exomethylene-D-glucopyranonucleosides with thymine, uraci... more A novel series of exomethylene-and keto-exomethylene-D-glucopyranonucleosides with thymine, uracil, and 5-fluorouracil as heterocyclic bases have been designed and synthesized. Wittig condensation of the 3-keto glucoside 1 gave the corresponding 1,2:5,6-di-O-isopropylidene-3-deoxy-3-methylene-D-glucofuranose (2), which after hydrolysis and acetylation led to the precursor 1,2,4,6-tetra-O-acetyl-3-deoxy-3methylene-D-glucopyranose (4).Compound 4 was condensed with silylated thymine, uracil, and 5-fluorouracil, respectively, deacetylated and acetalated to afford 1-(3 0-deoxy-4 0 ,6 0-O-isopropylidene-3 0-methylene-b-D-glucopyranosyl)pyrimidines 7a-c. Oxidation of the free hydroxyl group in the 2 0-position of the sugar moiety led to the formation of the labile 1-(3 0-deoxy-4 0 ,6 0-O-isopropylidene-3 0-methylene-b-D-glucopyranosyl-2 0-ulose)pyrimidines 8a-c. Finally, deisopropylidenation of the resulted derivatives 8a-c afforded the diol nucleosides 9a-c. The target keto-exomethylene analogs 9a-c were more cytostatic against a variety of tumor cell lines than the corresponding saturated-hydroxy-exomethylene derivatives 6. In particular, the 5-fluorouracil derivative 9c was highly cytostatic at an IC 50 (50% inhibitory concentration) ranging between 0.56 and 9.4 lg/mL, which was comparable to the free parental 5-fluorouracil base.
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Papers by Dimitri komiotis