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Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2, 3-d]pyrimidine 4', 5'-Didehydro-L-ascorbic Acid Derivatives


Gazivoda, Tatjana; Šokčević, Mario; Kralj, Marijeta; Šuman, Lidija; Pavelić, Krešimir; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Balzarini, Jan; Mintas, Mladen; Raić-Malić, Silvana
Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2, 3-d]pyrimidine 4', 5'-Didehydro-L-ascorbic Acid Derivatives // Journal of Medicinal Chemistry, 50 (2007), 17; 4105-4112 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2, 3-d]pyrimidine 4', 5'-Didehydro-L-ascorbic Acid Derivatives

Autori
Gazivoda, Tatjana ; Šokčević, Mario ; Kralj, Marijeta ; Šuman, Lidija ; Pavelić, Krešimir ; De Clercq, Erik ; Andrei, Graciela ; Snoeck, Robert ; Balzarini, Jan ; Mintas, Mladen ; Raić-Malić, Silvana

Izvornik
Journal of Medicinal Chemistry (0022-2623) 50 (2007), 17; 4105-4112

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
C-5 alkynylated pyrimidines; C-6 alkylfuro[2; 3-d]pyrimidines; L-ascorbic acid; antiviral and cytostatic activity evaluations

Sažetak
The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2, 3-d]pyrimidine derivatives (12-22) of L-ascorbic acid were synthesized by coupling of 5-iodouracil-4', 5'-didehydro-5', 6'-dideoxy-L-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of L-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 uM). Pyrimidine derivatives of L-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3-37 uM) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[2, 3-d]pyrimidine derivative (12) and 6-p-bromophenylfuro[2, 3-d]pyrimidine derivative (19) showed the highest cytostatic activity (IC50 = 4.5-20 uM), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 uM, respectively, for compounds 3 and 9) at a approximately 5-fold lower concentration than that required to show cytotoxicity.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
125-0982464-2922 - RAZVOJ NOVIH PROLIJEKOVA I LIJEKOVA PROTIV VIRUSA I RAKA (Mladen Mintas, )
125-0982464-2925 - Razvoj i primjena novih molekula u pozitron-emisijskoj tomografiji (PET) (Silvana Raić-Malić, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • Chemical Abstracts
  • Excerpta Medica
  • Index Medicus