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

Zrinka Rajić 1 , Marijana Končić 1 , Kristina Miloloža 1 , Ivana Perković 1 , Ivan Butula 1 , Franz Bucar 2 ,  and Branka Zorc 1
  • 1 Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
  • 2 Institut für Pharmazeutische Wissenschaften, Bereich Pharmakognosie Graz, Austria

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

Novel primaquine conjugates with non-steroidal anti-inlammatory 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 β-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.

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