Acta Pharm. 60 (2010) 325-337

full paper

Original research paper

Primaquine-NSAID twin drugs: Synthesis, radical scavenging, antioxidant and Fe²⁺ chelating activity

ZRINKA RAJIĆ, MARIJANA ZOVKO KONČIĆ, KRISTINA MILOLOŽA, IVANA PERKOVIĆ, IVAN BUTULA, FRANZ BUCAR and BRANKA ZORC

bzbz@pharma.hr

¹ Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia

² Institut für Pharmazeutische Wissenschaften, Bereich Pharmakognosie, Graz, Austria

Accepted August 26, 2010

Novel primaquine conjugates with non-steroidal anti-inflammatory drugs (PQ-NSAIDs, 4a-h) were prepared, fully chemically characterized and screened for radical scavenging and antioxidant activities. The synthetic procedure leading to twin drugs 4a-h involved two steps: i) preparation of NSAID benzotriazolides 3a-h from the corresponding NSAID (ibuprofen, ketoprofen, fenoprofen, ketoprofen hydroxy and methylene analogues, diclofenac or indomethacin) and benzotriazole carboxylic acid chloride (BtCOCl, 1), ii) reaction of intermediates 3a-h with PQ. The prepared PQ-NSAIDs exerted moderate activities in the DPPH free radical test and b-carotene-linoleic acid assay. Moreover, ketoprofen derivatives 4d and 4b demonstrated a notable Fe²⁺ chelating ability as well. On the other hand, negligible antiproliferative and antituberculotic effects of conjugates 4a-h were observed.

Keywords: primaquine, NSAID, twin drug, conjugate, radical scavenging, antioxidant activity, chelating ability