No abstract

New compounds are tested as inhibitors of lipid peroxidation.

9-Substituted (pyrazol-5-yl)methyl-or (2-pyrazolin-5-yl)methyl-9H-purines were synthesized from 9-allyl-6-chloro-9H-purine through the 1,3-dipolar cycloaddition reaction with nitrile imines, prepared in situ from the corresponding hydrazone and NBS/Et 3 N under MW or from hydrazinoylchloride and Et 3 N under reflux. The coupling of new 6-chloropurines with amines in H 2 O under microwaves resulted quantitatively to modified pyrazol-5-yl-or 2-pyrazolin-5-yl adenine homo-N-nucleosides. The new compounds were tested in vitro for their ability to: (i) interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH), (ii) inhibit lipid peroxidation, (iii) inhibit the activity of soybean lipoxygenase, (iv) inhibit in vitro thrombin and for (v) their antiproliferative and cytotoxic activity. Pyrazolines were found to be more potent in vitro. Compound 7a exhibited satisfactory combined antioxidant and anti-lipid peroxidation activity, inhibition of lipoxygenase (89%) and thrombin inhibitory ability, whereas compound 7b exhibited high lipoxygenase inhibitory activity in combination to significant anti-thrombin activity. No compound exhibited a significant cytotoxic activity, while all showed moderate antiproliferative activity.

No abstract

Στην παρούσα διατριβή διερευνήθηκε η σύνθεση και η μελέτη της δομής βιολογικά δραστικών ετεροκυκλικών συστημάτων πουρίνης με πενταμελείς, εξαμελείς και επταμελείς δακτυλίους. Συγκεκριμένα παρασκευάστηκαν τροποποιημένοι ομο-Ν-νουκλεοζίτες πουρινών με πυριδίνη, πυρρόλιο, αζεπίνη, διαζεπίνη, πυραζόλιο, πυραζολίνη, ισοξαζολίνη και οξαζεπίνη και μελετήθηκε η βιολογική τους δράση ως αναστολείς της λιποξυγονάσης, της λιπιδικής υπεροξείδωσης, με ταυτόχρονη αναστολή της θρομβίνης.