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Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis


Vujasinović, Ines; Paravić-Radičević, Andrea; Mlinarić-Majerski, Kata; Brajša, Karmen; Bertoša, Branimir
Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis // Bioorganic & medicinal chemistry, 20 (2012), 6; 2101-2110 doi:10.1016/j.bmc.2012.01.032 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis

Autori
Vujasinović, Ines ; Paravić-Radičević, Andrea ; Mlinarić-Majerski, Kata ; Brajša, Karmen ; Bertoša, Branimir

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 20 (2012), 6; 2101-2110

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

Ključne riječi
QSAR ; VolSurf+ ; pyrazole ; amidooxime ; antitumor activity ; A549 and NCIH23 lung cancer cells

Sažetak
Using literature data on anticancer activity of pyrazole derivatives, 3D-QSAR models were developed and 3D-QSAR analysis was performed. The 3D-QSAR analysis enabled identification of molecular properties that have the highest impact on antitumor activity against lung cancer cells. The results of 3D-QSAR analysis were taken into account while new compounds were designed. Obtained 3D-QSAR models were used for prediction of activity of new compounds. In this way, design of new compounds was guided by 3D-QSAR analysis which was performed on literature data. Ten new pyrazole derivatives were synthesised and their antitumor activities against A549 and NCIH23 lung cancer cells were validated. In order to obtain full profile of anticancer activity, cells viability (MTS) assays were combined with cell proliferation (BrdU) assays which measure actively dividing cells in treated sample. Experimental measurements showed good agreement between predicted and measured activities for majority of compounds. Also, anticancer activities of new pyrazole derivatives pointed to the chemical groups that can be useful in designing antitumor molecules. Substitution of hydrazine linker with rigid, 1, 2, 4-oxadiazole moiety resulted in compound 10, which has low (if any) cytotoxic activity and high potential cytostatic activity. Therefore, compound 10 presents a good starting point for design of new, more potent and safer anticancer therapeutics.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija



POVEZANOST RADA


Projekt / tema
098-0982933-2911 - Kavezasti spojevi: ugradbene jedinice u molekularnim sustavima (Kata Majerski, )
098-1191344-2860 - Proučavanje biomakromolekula računalnim metodama i razvoj novih algoritama (Sanja Tomić, )

Ustanove
Pliva-Istraživački institut,
Institut "Ruđer Bošković", 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


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