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

• Published in: Archiv der Pharmazie (Weinheim) 2016-02, Vol.349 (2), p.150-159
• Main Authors: Hameed, Alhamzah Dh, Ovais, Syed, Yaseen, Raed, Rathore, Pooja, Samim, Mohammed, Singh, Surender, Sharma, Kalicharan, Akhtar, Mymona, Javed, Kalim
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-proliferative activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Carrageenan; Cell Line, Tumor; COX-2; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Drug Screening Assays, Antitumor; Edema - chemically induced; Edema - drug therapy; Female; Humans; LOX-5 inhibitors; Male; Phthalazines - chemical synthesis; Phthalazines - chemistry; Phthalazines - pharmacology; Phthalazone; Rats, Wistar; Structure-Activity Relationship; Sulfones - chemical synthesis; Sulfones - chemistry; Sulfones - pharmacology
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201500336

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, 1H NMR, 13C 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. A library of new phthalazone compounds (2a–p) was synthesized as dual inhibitors (COX‐2/LOX‐5) and evaluated for their anti‐inflammatory, anticancer activities. Two compounds showed significant anti‐inflammatory activity comparable with that of the standard drug etoricoxib, whereas three compounds showed moderate sensitivity toward the renal cancer cell line UO‐31.