Novel Substituted Purine Isosteres: Synthesis,Structure-Activity Relationships and Cytotoxic Activity Evaluation |
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| Authors: | Spyridon Dimitrakis Efthymios-Spyridon Gavriil Athanasios Pousias Nikolaos Lougiakis Panagiotis Marakos Nicole Pouli Katerina Gioti Roxane Tenta |
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| Institution: | 1.Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Zografou, Greece; (S.D.); (E.-S.G.); (A.P.); (N.L.); (N.P.);2.Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University, 17671 Athens, Greece; (K.G.); (R.T.) |
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| Abstract: | A number of pyrrolo2,3-c]pyridines, pyrrolo3,2-d]pyrimidines and pyrazolo4,3-d]pyrimidines were designed and synthesized as antiproliferative agents. The target compounds possessed selected substituents in analogous positions on the central scaffold that allowed the extraction of interesting SARs. The cytotoxic activity of the new derivatives was evaluated against prostatic (PC-3) and colon (HCT116) cell lines, and the most potent analogues showed IC50 values in the nM to low µM range, while they were found to be non-toxic against normal human fibroblasts (WI-38). Flow cytometric analysis of DNA content revealed that the most promising derivative 14b caused a statistically significant accumulation of PC-3 cells at G2/M phase and induced apoptosis in PC-3 cells. |
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| Keywords: | purine isosteres pyrrolopyridine pyrrolopyrimidine pyrazolopyrimidine synthesis cytotoxic activity cell cycle perturbation apoptosis |
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