Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Tsoukala, Evangelia; Tzioumaki, Niki; Manta, Stella; Riga, Alexandra; Balzarini, Jan; Komiotis, Dimitri

doi:10.1016/j.bioorg.2010.08.001

Cited by 7 publications

(1 citation statement)

References 37 publications

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“…The antiviral assays were based on the inhibition of virus-induced cytopathicity in confluent cell cultures, and the cytostatic assays on inhibition of tumor cell proliferation in exponentially growing tumor cell cultures according to previously described methods [17]. The synthesized compounds were evaluated against the following viruses: herpes simplex virus type 1 (HSV-1) strain KOS, thymidine kinase-deficient (TK-) HSV-1 KOS strain resistant to ACV (ACV r ), herpes simplex virus type 2 (HSV-2) strain G, cytomegalovirus strains AD-169 and David, varicella zoster virus (VZV) strains OKA and YS, vaccinia virus Lederle strain, respiratory syncytial virus (RSV) strain Long, vesicular stomatitis virus (VSV), Coxsackie B4 virus, parainfluenza 3 virus, influenza virus A (subtypes H1N1, H3N2), influenza virus B, reovirus-1, Sindbis and Punta Toro virus.…”

Section: Antiviral Activity Assaymentioning

confidence: 99%

Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

et al. 2019

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Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC 50 = 13 -27 mg/mL for strain H1N1 and 9.3 -18 mg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC 50 = 0.3 mg/mL for Ig and 1.9 mg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC 50 of 0.30, 0.70 and 2.50 mg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies.

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Section: Antiviral Activity Assaymentioning

confidence: 99%

Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

et al. 2019

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Branched-chain C-cyano pyranonucleosides: Synthesis of 3′-C-cyano & 3′-C-cyano-3′-deoxy pyrimidine pyranonucleosides as novel cytotoxic agents

Kiritsis

Manta

Parmenopoulou

et al. 2011

European Journal of Medicinal Chemistry

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This report describes the total and facile synthesis of 3'-C-cyano & 3'-C-cyano-3'-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-α-D-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'-C-cyano-β-D-glucopyranosyl)nucleosides 6a-d. Routine deoxygenation at position 3' 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'-C-cyano-3'-deoxy-β-D-allopyranosyl)nucleosides 12a-d. 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.

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Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities

Karaküçük‐İyidoğan

Tasdemir

Oruç‐Emre

et al. 2011

European Journal of Medicinal Chemistry

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a b s t r a c tA series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UVeVis, IR, 1 H NMR, 13 C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners.

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Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

Cited by 7 publications

References 37 publications

Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

Branched-chain C-cyano pyranonucleosides: Synthesis of 3′-C-cyano & 3′-C-cyano-3′-deoxy pyrimidine pyranonucleosides as novel cytotoxic agents

Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities

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