Next Article in Journal
A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations
Previous Article in Journal
Old and New Biological Therapies for Psoriasis
Open AccessArticle

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases

1
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia
2
Department of Biotechnology, Center for High-Throughput Technologies, University of Rijeka, Ulica Radmile Matejčić 2, HR-51000 Rijeka, Croatia
3
Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, HR-10000 Zagreb, Croatia
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(11), 2292; https://doi.org/10.3390/ijms18112292
Received: 13 September 2017 / Revised: 18 October 2017 / Accepted: 25 October 2017 / Published: 1 November 2017
(This article belongs to the Section Bioactives and Nutraceuticals)
A series of mono-pyrrolo[2,3-d]pyrimidines 4a4k, unsymmetrical bis-purine isosteres 5a5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1) cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9)/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma) and p38 MAP (mitogen-activated protein) kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer. View Full-Text
Keywords: pyrrolo[2,3-d]pyrimidines; purinomimetics; 1,2,3-triazole; anticancer; pancreatic carcinoma (CFPAC-1) pyrrolo[2,3-d]pyrimidines; purinomimetics; 1,2,3-triazole; anticancer; pancreatic carcinoma (CFPAC-1)
Show Figures

Graphical abstract

MDPI and ACS Style

Bistrović, A.; Harej, A.; Grbčić, P.; Sedić, M.; Kraljević Pavelić, S.; Cetina, M.; Raić-Malić, S. Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases. Int. J. Mol. Sci. 2017, 18, 2292. https://doi.org/10.3390/ijms18112292

AMA Style

Bistrović A, Harej A, Grbčić P, Sedić M, Kraljević Pavelić S, Cetina M, Raić-Malić S. Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases. International Journal of Molecular Sciences. 2017; 18(11):2292. https://doi.org/10.3390/ijms18112292

Chicago/Turabian Style

Bistrović, Andrea; Harej, Anja; Grbčić, Petra; Sedić, Mirela; Kraljević Pavelić, Sandra; Cetina, Mario; Raić-Malić, Silvana. 2017. "Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases" Int. J. Mol. Sci. 18, no. 11: 2292. https://doi.org/10.3390/ijms18112292

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop