Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of 5-alkyl-2'-deoxyuridine 3',5'-cyclic monophosphates (5-R-cdUMP's, R = Et, i-Pr, n-Pr, n-Bu, n-Pent, n-Hex, n-Oct) was prepared and tested in culture systems as antitumor and antiviral agents in comparison to the 5-alkyl-2'-deoxyuridines (5-R-dUrd's) themselves. Only the 5-Et- and 5-n-Bu-cdUMP showed appreciable cytostatic activities against murine L1210 and human lymphoblast Raji cells (ID50 range: 28-82 micrograms/mL). 5-Et-dUrd itself was much more active (ID50 = 1.6 and 2.9 micrograms/mL). The 5-i-Pr-, and 5-n-Bu-dUrd's were inactive, but activity increased again for groups with chain lengths of five carbons or greater. 5-Et-cdUMP and 5-Et-dUrd had greatly reduced activities against deoxythymidine kinase deficient (TK-) L1210 and Raji cells. 5-Et-cdUMP evidently is not an efficient prodrug source of the corresponding 5'-monophosphate where the TK- cells are concerned. Of the 5-R-cdUMP's, 5-Et-cdUMP displayed reasonably good antiviral potency against herpes simplex types 1 and 2 (MIC50, mostly 7-70 micrograms/mL) and vaccinia virus (MIC, 70 micrograms/mL). The activity was nonetheless 10- to 100-fold less than that for 5-Et-dUrd. The other 5-R-dUrd's generally showed decreasing antiviral activity with increasing 5-R chain length. Methyl and/or benzyl neutral triesters of certain 5-R-cdUMP's were inactive as antivirals and largely inactive against tumor cells in culture. In contrast to the 5'-monophosphates, the 5-R-cdUMP's failed to inhibit thymidylate synthetase from L1210 cells.
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PMID:Synthesis and antitumor and antiviral properties of 5-alkyl-2'-deoxyuridines, 3',5'-cyclic monophosphates, and neutral cyclic triesters. 395 27

As a continuation of our previous efforts on N-alkyl/aryl-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and N-alkyl/aryl-N'-[4-(3-aralkylthio-4-alkyl/aryl-4H-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, a series of novel 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 23-26 and several related thioureas, N-alkyl/aryl-N'-{4-[(4-alkyl/aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methoxy]phenyl}thioureas 27-42 were synthesized for evaluation of their antiviral potency. Structures of the synthesized compounds were confirmed by the use of (1)H NMR, (13)C NMR and HR-MS data. All compounds 1-42 were evaluated in vitro against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT-4 cells, as well as other selected viruses such as HSV-1, HSV-2, Coxsackie virus B4, Sindbis virus and Varicella-zoster virus using HeLa, Vero, HEL and E6SM cell cultures, and anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv. Compounds 4 and 5 showed weak activity against HSV-1, HSV-2 and TK(-) HSV, whereas eight compounds showed marginal activity against Coxsackie virus B4. The most active derivative in this series was compound 38 which showed moderate protection against Coxsackie virus B4 with an MIC value of 16 microg/ml and a selectivity index of 5. This compound was also active against thymidine kinase positive Varicella-zoster virus (TK(+) VZV, OKA strain) with an EC(50) value of 9.9 microg/ml. Compound 38 was the most active compound with 79% inhibition against M. tuberculosis H37Rv.
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PMID:Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis agents. 1758 88

The synthesis of dideoxy-6-azathymidine 4'-thionucleoside 1-(2,3-dideoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4-thio-beta-L-erythro-pentofuranosyl)-(6-azathymidine) (3) and their evaluation against a wide panel of antiviral assays are described. The L-thionucleoside (3) was devoid of antiviral activity. The dideoxy-thionucleoside (2) was moderately active against vaccinia virus (VV) and the herpes simplex virus strains HSV-1 (strain KOS) and HSV-2 (strain G) (MIC 12 microM) and retained inhibitory activity vs a thymidine kinase-deficient strain HSV-1/TK(-), suggesting that (2) is not dependent on viral TK-catalysed phosphorylation for antiviral activity and/or may use an alternative metabolic activation pathway.
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PMID:6-Azathymidine-4'-thionucleosides: synthesis and antiviral evaluation. 1834 Dec 54