Synthesis and Biological Evaluation of New Phthalazinone Derivatives as Anti‐Inflammatory and Anti‐Proliferative Agents

Abstract

The chemistry of phthalazine derivatives has been of increasing interest since many of these compounds have found many chemotherapeutic applications. So this study aims to synthesize a library of phthalazine derivatives and to investigate their anti-inflammatory and anti-proliferative activities. Sixteen new phthalazinone derivatives (2a-p) were synthesized and tested for their in vitro antiproliferative and in vivo anti-inflammatory activities. All the synthesized compounds were identified and characterized by IR, (1) H NMR, (13) C NMR spectroscopy, and MS. Two compounds, 2b and 2i, showed significant anti-inflammatory activity comparable with that of the standard drug etoricoxib in the carrageenan-induced rat paw edema model at 3 and 5 h, respectively. Three compounds (2h, 2j, and 2g) showed moderate sensitivity toward the renal cancer cell line UO-31.

Pharmacological activities of various phthalazine and phthalazinone derivatives

“…Some compounds, showed significant anti-inflammatory activity comparable with that of the standard drug etoricoxib in the carrageenan-induced rat paw edema model. Some compounds showed moderate sensitivity toward the renal cancer cell line UO-31 (Hameed et al, 2016).…”

Recent development of lipoxygenase inhibitors as anti-inflammatory agents

“…Compound 36 was found to exhibit the best activity (IC 50 = 6.2 μM) in this series in a carrageenan-induced rat paw edema model. 71 In 2016, based on these three pharmacophores of sulfonyl group, thiazole ring and pyrazole ring, Abdelall and coworkers designed and synthesized a series of 1,5diarylpyrazoline derivatives, and further evaluated their inhibitory potency against 15-LOX. 72 In this series, compound 37 showed the best potency with an IC 50 value of 4.7 μM.…”

Synthesis and Investigation of Phthalazinones as Antitubercular Agents

“…Phthalazinones exhibit ad iverse range of pharmaceutical properties, such as anti-cancer, [1][2][3] anti-inflammatory, [4][5][6] anti-bacterial, [1,7] anti-oxidant, [1] and anti-neurodegenerative [8] properties, with mechanismso fa ction that are as varied as the diseases they are used against. [9][10][11][12] For example, the clinically used anticancer drug oliparib (1,F igure 1) inhibits the poly(ADP-ribose)polymerase, [9] while azelastine (2)i sa na ntihistamine preferentially taken up by lung and alveolar macrophages.…”