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Ruthenium(II) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines

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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of molecules which have been found to be active against cancer cells with chemopreventive properties by targeting cyclooxygenase (COX-1 and COX-2) and lipoxygenase (LOX), commonly upregulated (particularly COX-2) in malignant tumors. Arene ruthenium(II) complexes with a pseudo-octahedral coordination environment containing different ancillary ligands have shown remarkable activity against primary and metastatic tumors as reported earlier. This work describes the synthesis of four novel ruthenium(II)–arene complexes viz. [Ru(η6-p-cymene)(nap)Cl] 1 [Hnap = naproxen or (S)-2-(6-methoxy-2-naphthyl)propionic acid], [Ru(η6-p-cymene)(diclo)Cl] 2 [Hdiclo = diclofenac or 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, [Ru(η6-p-cymene)(ibu)Cl] 3 [Hibu = ibuprofen or 2-(4-isobutylphenyl)propanoic acid] and [Ru(η6-p-cymene)(asp)Cl] 4 [Hasp = aspirin or 2-acetoxy benzoic acid] using different NSAIDs as chelating ligands. Complexes 1–3 have shown promising antiproliferative activity against three different cell lines with GI50 (concentration of drug causing 50% inhibition of cell growth) values comparable to adriamycin. At the concentration of 50 μM, complex 3 is more effective in the inhibition of cyclooxygenase and lipooxygenase enzymes, followed by complex 2 and complex 1 in comparison to their respective free NSAID ligands indicating a possible correlation between the inhibition of COX and/or LOX and anticancer properties. Molecular docking studies with COX-2 reveal that complexes 1 and 2 having naproxen and diclofenac ligands exhibit stronger interactions with COX-2 than their respective free NSAIDs and these results are in good agreement with their relative experimentally observed COX inhibition as well as anti-proliferative activities.

Graphical abstract: Ruthenium(ii) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines

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Publication details

The article was received on 27 Sep 2017, accepted on 19 Nov 2017 and first published on 28 Nov 2017


Article type: Paper
DOI: 10.1039/C7DT03637J
Citation: Dalton Trans., 2018, Advance Article
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    Ruthenium(II) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines

    P. Mandal, B. K. Kundu, K. Vyas, V. Sabu, A. Helen, S. S. Dhankhar, C. M. Nagaraja, D. Bhattacherjee, K. P. Bhabak and S. Mukhopadhyay, Dalton Trans., 2018, Advance Article , DOI: 10.1039/C7DT03637J

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