Publications (7)16.71 Total impact
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Article: Novel 1,2,4-triazole and imidazole derivatives of L-ascorbic and imino-ascorbic acid: synthesis, anti-HCV and antitumor activity evaluations.
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ABSTRACT: Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 ± 4 and 7.3 ± 0.1 μM, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead.Bioorganic & medicinal chemistry 02/2012; 20(11):3675-85. · 2.82 Impact Factor -
Article: Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity.
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ABSTRACT: We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3 - 6 ), 4,5-dicyanoimidazole (compound 7 ), and purine (compounds 8 - 13 ) coumarin derivatives and their acyclic nucleoside analogues 14 - 18 . Structures of novel compounds 3 - 18 were deduced from their <sup>1</sup>H- and <sup>13</sup>C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC<sub>50</sub> = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC<sub>50</sub> = 33 µM), HepG2 (IC<sub>50</sub> = 25 µM) and SW620 (IC<sub>50</sub> = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.Molecules 01/2012; 17(9):11010-25. · 2.39 Impact Factor -
Article: Evaluation of in vitro biological activity of O-alkylated hydroxamic derivatives of some nonsteroidal anti-inflammatory drugs.
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ABSTRACT: Several published studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. This study examined the in vitro effect of O-alkylated NSAID hydroxamic acid derivatives 3a-i on cell survival for a panel of human tumour cell lines, their cytotoxicity on normal human fibroblasts and their antiviral activity. Established methods of cell viability testings, cell cycle analyses and Western blot assays were used. O-Alkylated NSAID hydroxamic acid derivatives exerted poor antiviral activity butreduced the viability of the studied tumour cell lines in a concentration-dependent manner showing low cytotoxic effect on normal fibroblasts. Compounds 3a and 3i were shown to be potent inhibitors of the growth of MIA PaCa-2 cell line. They induced p53-independent S-phase arrest and triggered caspase 3-dependent apoptosis. Two novel O-alkylated NSAID hydroxamic acid derivatives may be useful in the treatment of pancreatic cancer and should be further evaluated in vivo.Anticancer research 10/2010; 30(10):3987-94. · 1.73 Impact Factor -
Article: The unsaturated acyclic nucleoside analogues bearing a sterically constrained (Z)-4'-benzamido-2'-butenyl moiety: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations.
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ABSTRACT: A series of the novel acyclic unsaturated pyrimidine (1-12) and adenine (13) nucleoside analogues bearing conformationally restricted (Z)-2'-butenyl moiety were synthesized and evaluated for their antiviral and cytostatic activity potency against malignant tumor cell lines and normal human fibroblast (WI38). The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3 substituted 5-trifluoromethyluracil derivative (11), N-1, N-3 disubstituted 5-fluorouracil derivative (12) and adenine derivative (13) was deduced from their (1)H and (13)C NMR spectra and confirmed by single crystal X-ray structure analysis. The X-ray crystal structure analysis 11-13 revealed also supramolecular self-assemblies, in which infinite chains or dimers built two- and three-dimensional networks. The results of the in vitro cytostatic activity evaluations of 1-13 indicate that the majority of the compounds tested exhibited a non-specific and moderate antiproliferative effect at the highest concentration (100 microM). Of all evaluated compounds on the cell lines tested only the N-1 4''-fluoro-substituted-benzamide uracil derivative (7) showed rather marked and selective inhibitory activity against the growth of MCF-7 cells at a concentration of 2.7 microM and no cytotoxic effect on normal fibroblasts WI38. This compound can be therefore considered as a potential antitumor lead compound for further synthetic structure modification.Bioorganic & medicinal chemistry 09/2010; 18(17):6249-57. · 2.82 Impact Factor -
Article: Novel cyano- and amidino-substituted derivatives of styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines. Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation, part 3.
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ABSTRACT: Synthesis of novel cyano- and amidino-substituted styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines by condensation reactions and photochemical dehydrocyclization and dehydrohalogenation cyclization is described. Thermal denaturation experiments reveal that cyclic derivatives considerably stabilize DNA double helix, while the effect of their acyclic analogues is negligible. According to the spectroscopic study of the interaction of cyclic derivative 19, we propose intercalation of benzimidazo[1,2-a]quinoline moiety into ct-DNA as a dominant interaction underlying biologically relevant effects of this compound, whereas for its acyclic derivative 11, we propose binding into the minor groove of DNA. All compounds show noticeable antiproliferative effect. Morpholino- and chloro-substituted compound 9 is the most active among all acyclic derivatives. All cyclic compounds were 2- to 10-fold more potent, which is correlated with their property to intercalate into DNA. The most active imidazolyl-substituted compound 19 inhibits topoisomerase II and induces strong G2/M cell cycle arrest, pointing to the impairment in mitotic progression. Its pronounced selectivity toward colon carcinoma cells encourages further development of this compound as a lead.Journal of Medicinal Chemistry 12/2007; 50(23):5696-711. · 5.25 Impact Factor -
Article: Novel Cyano- and Amidino-Substituted Derivatives of Styryl-2Benzimidazoles and Benzimidazo[1,2- a ]quinolines. Synthesis, Photochemical Synthesis, DNA Binding, and Antitumor Evaluation, Part 3
Journal of Medicinal Chemistry - J MED CHEM. 01/2007; 50(23):5696-5711. -
Article: Global approach to perinatal medicine: functional genomics and proteomics.
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ABSTRACT: Functional genomics (transcriptomics and proteomics) is a global, systematic and comprehensive approach to the identification and description of the processes and pathways involved in normal and abnormal physiological states. The functional genomics methods most applied today are DNA microarrays and proteomics methods, primarily two-dimensional gel electrophoresis coupled with mass spectrometry. To date, interesting research has been carried out, representing milestones for future implementation of functional genomics/proteomics in perinatal medicine. For instance, possible biomarkers of pre-eclampsia, preterm labor and gestational trophoblastic diseases have been discovered. Further systematic examination of differentially regulated genes and proteins in maternal and fetal tissues and fluids will be required. However, high-throughput technologies reflect biological fluctuations and methodological errors. Large amounts of such different data challenge the performance and capacity of the statistical tools and software available at present. Further major developments in this field are pending and the intellectual investment will certainly result in clinical advances.Journal of Perinatal Medicine 02/2005; 33(1):5-16. · 1.70 Impact Factor -
Article: Novosti u mozaiku metastaziranja zloćudnih tumora
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ABSTRACT: Despite the abundance of attention that cancer has attracted, it continues to constitute one of the deadliest scourges of the modern era. Tumour heterogeneity greatly contributes to the ineffectiveness of current therapies and hampers the study and treatment of cancer. There are two models accounting for tumour heterogeneity and propagation, namely clonal evolution model and cancer stem cell model. In particular, cancer stem theory has attracted much attention lately, as these cells with self-renewal and differentiation abilities are responsible for the initiation of tumour development, growth, and its ability to metastasize and reoccur, and provide a reasonable explanation for poor prognosis for patients in advanced stages of solid tumours. Advances in technologies such as proteomics open new avenues in metastasis research by specifically revealing complex protein networks involved in tumour progression, which should facilitate early diagnosis and provide the basis for designing more effective treatment strategies.Rad. Medical sciences; No.508=35.
Top co-authors
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Institutions
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2010–2012
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University of Zagreb
- Faculty of Chemical Engineering and Technology (FKIT)
Zagreb, Grad Zagreb, Croatia -
University of Rijeka
- Department of Biotechnology
Rijeka, Primorsko-Goranska Zupanija, Croatia
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