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Screening of potential prodrugs on cells derived from Dupuytren’ s Disease patients


Kraljević Pavelić, Sandra; Bratulić, Siniša; Hock, Karlo; Jurišić, Davor; Hranjec, Marijana; Karminski-Zamola, Grace; Žinić, Biserka; Bujak, Maro; Pavelić, Krešimir
Screening of potential prodrugs on cells derived from Dupuytren’ s Disease patients // Biomedicine and Pharmacotherapy, 63 (2009), 8; 577-585 (međunarodna recenzija, članak, znanstveni)


Naslov
Screening of potential prodrugs on cells derived from Dupuytren’ s Disease patients

Autori
Kraljević Pavelić, Sandra ; Bratulić, Siniša ; Hock, Karlo ; Jurišić, Davor ; Hranjec, Marijana ; Karminski-Zamola, Grace ; Žinić, Biserka ; Bujak, Maro ; Pavelić, Krešimir

Izvornik
Biomedicine and Pharmacotherapy (0753-3322) 63 (2009), 8; 577-585

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

Ključne riječi
Dupuytren's contracture; fibroblasts; myofibroblasts

Sažetak
Dupuytren’s Disease (DD) is a fibroproliferative disorder, the cure for which is still limited to surgical excision of the affected fascia, often leading to high recurrence rates. Due to this fact, non-surgical treatments are being investigated, among them those targeting molecular processes of proliferation and differentiation in Dupuytren’ s cell cultures. Drugs with antiproliferative action may be valuable in DD treatment. Through characterization of changes on DD-specific cells, we therefore decided to test the therapeutic potential of new cytostatic drugs for DD treatment and/or for reduction of post-operative recurrence rates. The N-sulphonylpyrimidine derivative, amidino-substituted benzimidazo[1, 2-a]quinoline, and amidino dihydrothienothienyl[2, 3-c]quinolone hydrochloride, known to affect proliferation processes, were tested for their antiproliferative activity on primary fibroblasts/myofibroblasts cell cultures derived from the palmar fascia of patients with DD. Only amidino dihydrothienothienyl[2, 3-c]quinolone hydrochloride acted in a highly specific manner on cells derived from diseased fascia of DD patients and exhibited a low cytotoxic effect. This result might be a consequence of its specific activity on cytoskeleton changes occurring in differentiating cells. A similar short-term differential antiproliferative effect was observed by the N-sulphonylpyrimidine derivative that was however completely lost after 6- and 14-day treatments. The amidino-substituted benzimidazo[1, 2-a]quinoline exerted a strong non-specific, dose-related antiproliferative activity on cell types.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )
098-0982914-2935 - Sinteza novih biološki aktivnih derivata nukleobaza i nukleotida (Biserka Žinić, )
125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni ("pametni") lijekovi (Marijana Hranjec, )
14V09809

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