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Pregled bibliografske jedinice broj: 775301

Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations


Stipković Babić, Maja; Makuc, Damjan; Plavec, Janez; Martinović, Tamara; Kraljević Pavelić, Sandra; Pavelić, Krešimir; Snoeck, Robert; Andrei, Graciela; Schols, Dominique; Wittine, Karlo; Mintas, Mladen
Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations // European journal of medicinal chemistry, 102 (2015), 288-302 doi:10.1016/j.ejmech.2015.08.008 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations

Autori
Stipković Babić, Maja ; Makuc, Damjan ; Plavec, Janez ; Martinović, Tamara ; Kraljević Pavelić, Sandra ; Pavelić, Krešimir ; Snoeck, Robert ; Andrei, Graciela ; Schols, Dominique ; Wittine, Karlo ; Mintas, Mladen

Izvornik
European journal of medicinal chemistry (0223-5234) 102 (2015); 288-302

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

Ključne riječi
3-Deazapurines; 7-Deazapurines; 9-Deazapurines; L-Ascorbic acid; Imino-L-ascorbic acid; Cytostatic activity; Antiviral activity

Sažetak
Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and L-ascorbic acid (L-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of L-ascorbic(1-4, 8-10, 13-15) and imino-L-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of L-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 ± 1.8 μM) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 ± 0.1 μM) while the 9-deazahypoxanthine derivative of L-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 ± 1.3 μM)and prominent effect on L1210/0 (IC50 = 4.5 ± 0.5 μM). Furthermore, the 9-deazapurine derivative disubstituted with two imino-L-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 ± 0.3 μM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 ± 0.2 μM). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of L-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
125-0982464-2922 - RAZVOJ NOVIH PROLIJEKOVA I LIJEKOVA PROTIV VIRUSA I RAKA (Mladen Mintas, )
335-0000000-3532 - Uloga IGF2 i signalni putovi nizvodno u karcinomima pluća čovjeka (Sandra Kraljević Pavelić, )
335-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )

Ustanove
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Sveučilište u Rijeci - Odjel za biotehnologiju

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


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