Title:Chalcones as Potential Cyclooxygenase-2 Inhibitors: A Review
Volume: 24
Issue: 2
Author(s): Mohammad Mahboubi-Rabbani, Rosa Zarei, Mehdi Baradaran, Maryam Bayanati and Afshin Zarghi*
Affiliation:
- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
Keywords:
Chalcones, COX-2 inhibitors, prostaglandins, inflammation, cancer, neurodegenerative diseases.
Abstract: Cyclooxygenases (COXs) play a pivotal role in inflammation, a complex phenomenon required in
human defense, but also involved in the emergence of insidious human disorders. Currently-used COX-1 inhibitors
(Non-Steroidal Anti-Inflammatory Drugs-NSAIDs), as the most frequent choices for the treatment of chronic
inflammatory diseases, have been identified to be associated with a variety of adverse drug reactions, especially
dyspepsia, as well as peptic ulcer, which lead to diminished output. Moreover, the structural similarities of COX-
1 and -2, along with the availability of comprehensive information about the three-dimensional structure of COX-
2, co-crystallized with various inhibitors, search selective COX-2 inhibitors a formidable challenge. COX-2 inhibitors
were shown to minimize the incidence of metastasis in cancer patients when administered preoperatively.
Developing selective COX-2 inhibitors to tackle both cancer and chronic inflammatory illnesses has been identified
as a promising research direction in recent decades. Identifying innovative scaffolds to integrate as the major
component of future COX-2 inhibitors is critical in this regard. The presence of a central, α, β-unsaturated carbonyl-
containing scaffold, as a characteristic structural pattern in many selective COX-2 inhibitors, along with a
huge count of chalcone-based anticancer agents representing the basic idea of this review; providing a survey of
the most recently published literature concerning development of chalcone analogs as novel COX-2 inhibitors
until 2022 with efficient anticancer activity. A brief overview of the most recent developments concerning structure-
activity relationship insights and mechanisms is also reported, helping pave the road for additional investigation.
