Cyclooxygenase-2 (COX-2) as a Target of Anticancer Agents: A Review of Novel Synthesized Scaffolds Having Anticancer and COX-2 Inhibitory Potentialities

Abstract

Cancer is a serious threat to human beings and is the second-largest cause of death all over the globe. Chemotherapy is one of the most common treatments for cancer; however, drug resistance and severe adverse effects are major problems associated with anticancer therapy. New compounds with multi-target inhibitory properties are targeted to surmount these challenges. Cyclooxygenase-2 (COX-2) is overexpressed in cancers of the pancreas, breast, colorectal, stomach, and lung carcinoma. Therefore, COX-2 is considered a significant target for the synthesis of new anticancer agents. This review discusses the biological activity of recently prepared dual anticancer and COX-2 inhibitory agents. The most important intermolecular interactions with the COX-2 enzyme have also been presented. Analysis of these agents in the active area of the COX-2 enzyme could guide the introduction of new lead compounds with extreme selectivity and minor side effects.

Antiproliferative and anti‐inflammatory effects of fractionated crude lectins from boiled kidney beans (Phaseolus vulgaris)

“…IL‐1β is secreted by immune and cancer cells or other cells and has anti‐cancer or pro‐cancer effects, depending on the cell type (Rebe & Ghiringhelli, 2020). Cyclooxygenase‐2 (COX‐2) is typically expressed during host exposure to inflammatory and other physiological stimuli and growth factors but is also known to be overexpressed in many cancers (Mohsin et al., 2022).…”

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

“…An increased COX-II level has been observed in colorectal, breast, liver, pancreatic, esophageal, and lung cancer, and in melanoma. [4] NSAIDs are frequently used for the management of cancer-related pain and inflammation. The inhibition of COX-II by some NSAIDs has led to the inhibition of the process of cancer and the induction of metastasis.…”

“…COX‐II has a vital role in the initiation of cancer because it inhibits apoptosis and starts the process of angiogenesis. An increased COX‐II level has been observed in colorectal, breast, liver, pancreatic, esophageal, and lung cancer, and in melanoma [4] . NSAIDs are frequently used for the management of cancer‐related pain and inflammation.…”

New paracetamol hybrids as anticancer and COX‐2 inhibitors: Synthesis, biological evaluation and docking studies

“…Nitrogen‐containing heterocycles present in several drugs or lead molecules have shown dual COX‐2 inhibitory and antiproliferative activities indicating COX‐2 inhibition as a promising adjuvant therapy to prevent proliferation of cancer cells. [ 27 ] For instance, licofelone and darbufelone have exhibited good COX‐2 inhibition and anticancer activity in breast and colon cells by triggering apoptosis; [ 28,29 ] indole derivative ( I ) [ 30 ] and 1,2,4‐triazole hybrid ( II ) [ 31 ] displayed dual anticancer and COX‐2 inhibitory effects. Compounds with 1,2,3‐triazole framework were also found to be antiproliferative by inhibiting COX‐2 such as hybrid ( III ) effectively suppresses COX‐2 with (half‐maximal inhibitory concentration [IC 50 ] 0.12 μM) and cytotoxic (IC 50 8.17 μM) on prostate cancer cells, [ 32 ] while compound IV inhibited both COX‐2 and cell proliferation via induction of apoptosis by increasing caspase‐9, Bax and decreasing Bcl‐2 levels in liver, breast, and lung cancers.…”