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

Alhamzah Dh Hameed; Syed Ovais; Raed Yaseen; Pooja Rathore; Mohammed Samim; Surender Singh; Kalicharan Sharma; Mymona Akhtar; Kalim Javed

doi:10.1002/ardp.201500336

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

Arch Pharm (Weinheim). 2016 Feb;349(2):150-9. doi: 10.1002/ardp.201500336. Epub 2016 Jan 3.

Authors

Alhamzah Dh Hameed¹, Syed Ovais¹, Raed Yaseen¹, Pooja Rathore¹, Mohammed Samim¹, Surender Singh², Kalicharan Sharma³, Mymona Akhtar³, Kalim Javed¹

Affiliations

¹ Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
² Department of Pharmacology, All India Institute of Medical Science, New Delhi, India.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Drug Design and Medicinal Chemistry Laboratory, Jamia Hamdard (Hamdard University), New Delhi, India.

PMID: 26725221
DOI: 10.1002/ardp.201500336

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.

Keywords: Anti-inflammatory activity; Anti-proliferative activity; COX-2; LOX-5 inhibitors; Phthalazone.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Carrageenan
Cell Line, Tumor
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
Male
Phthalazines / chemical synthesis
Phthalazines / chemistry*
Phthalazines / pharmacology
Rats, Wistar
Structure-Activity Relationship
Sulfones / chemical synthesis
Sulfones / chemistry*
Sulfones / pharmacology

Substances

2-(4-methanesulfonylphenyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1-one
4-(4-biphenyl)-2-(4-(methylsulfonyl)phenyl)phthalazin-1(2H)-one
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Cyclooxygenase 2 Inhibitors
Phthalazines
Sulfones
Carrageenan