A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines.

Introduction: Imidazo[1,2-]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines.

Methods: We evaluated the interaction between imidazo[1,2-]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies.

Design, Synthesis, and Evaluation of New Imidazo[1,2-]pyridine Derivatives as Cyclooxygenase-2 Inhibitors.

Background: Cyclooxygenase-2 (COX-2), the key enzyme in the arachidonic acid conversion to prostaglandins, is one of the enzymes associated with different pathophysiological conditions, such as inflammation, cancers, Alzheimer's, and Parkinson's disease. Therefore, COX-2 inhibitors have emerged as potential therapeutic agents in these diseases.

Objective: The objective of this study was to design and synthesize novel imidazo[1,2-a]pyridine derivatives utilizing rational design methods with the specific aim of developing new potent COX-2 inhibitors.

Design, synthesis, and biological evaluation of new 2-(4-(methylsulfonyl)phenyl)--phenylimidazo[1,2-]pyridin-3-amine as selective COX-2 inhibitors.

Cyclooxygenase (COX), which plays a role in converting arachidonic acid to inflammatory mediators, could be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). Although potent NSAIDs are available for the treatment of pain, fever, and inflammation, some side effects, such as gastrointestinal ulcers, limit the use of these medications. In recent years, selective COX-2 inhibitors with a lower incidence of adverse effects attained an important position in medicinal chemistry.

Novel Benzo[4,5]imidazo[1,2-]pyrimidine derivatives as selective Cyclooxygenase-2 Inhibitors: Design, synthesis, docking studies, and biological evaluation.

The present study was aimed at the synthesis and evaluation of a new series of benzo[4,5]imidazo[1,2-]pyrimidine having a methylsulfonyl group as COX-2 (cyclooxygenase-2) inhibitor pharmacophore. Molecular modeling studies were performed using the Autodock program, and the results demonstrated that methylsulfonyl pharmacophore was adequately placed into the COX-2 active site. The in vitro and in vivo COX-2 inhibitory effects were also evaluated.

Naringenin enhances anti-proliferation effect of 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one on two different cells via targeting calmodulin signaling pathway.

Background: FMSP is a synthesized ferrocene derivative with anti-cancer characteristics on tumor cells. Naringenin is a polyphenolic flavonoid with anti-tumor ability.

Methods: Cell viability and proliferation of two cancer cells and a normal cell line after treatment with these agents were determined with MTT assay.

Assessment of cytotoxic effects of new derivatives of pyrazino[1,2-a] benzimidazole on isolated human glioblastoma cells and mitochondria.

Aims: Glioblastoma multiforme (GBM) is a highly devastating malignant brain tumor with poor pharmacotherapy. Based on COX-2 inhibitory effects in preventing cancer progression, new pyrazino[1,2-a]benzimidazole derivatives were assessed on isolated human GBM cells.

Main Methods: In this study, firstly, primary culture of astrocytes from human GBM samples was prepared and exposed to 2,6-dimethyl pyrazino[1,2-a]benzimidazole (L1) and 3,4,5-trimethoxy pyrazino[1,2-a]benzimidazole (L2) for finding their half-maximal inhibitory concentration (IC).

4-(1-Benzyl-1-benzo[]imidazol-2-yl)-4-oxo-2-butenoic Acid Derivatives: Design, Synthesis and Anti-HIV-1 Activity.

Acquired immunodeficiency syndrome (AIDS) is still an incurable disease with increasing mortality rate. Despite the development of effective FDA-approved anti-HIV drugs, there are some problems due to the growing of resistant viral strands. Therefore, discovery of novel anti-HIV agents is so needed.

Evaluation of Cytotoxic Potentials of Novel Cyclooxygenase-2 Inhibitor against ALL Lymphocytes and Normal Lymphocytes and Its Anticancer Effect through Mitochondrial Pathway.

In the present study, we searched selective cytotoxicity and mitochondria mediated apoptosis of novel COX-2 inhibitor 2-(4-(Methylsulfonyl)phenyl)imidazo[1,2-] pyridine-8-carboxylic acid on B-lymphocytes and their mitochondria isolated from normal subjects and acute lymphoblastic leukemia (ALL) patients' blood. Our results showed this compound can selectively induce cellular and mitochondrial toxicity on ALL B-lymphocytes and mitochondria without any toxic effects on normal B-lymphocytes and their mitochondria. Taken together, the results of this study suggest that cancerous mitochondria are a potential target for the ALL B-lymphocytes.

Design, synthesis, and biological evaluation of new 1,4-diarylazetidin-2-one derivatives (β-lactams) as selective cyclooxygenase-2 inhibitors.

A new series of 1,4-diarylazetidin-2-one derivatives (β-lactams) were designed and synthesized to evaluate their biological activities as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC values in the 0.05-0.

Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors.

A new series of imidazo[2,1-b]thiazole analogs containing a methyl sulfonyl COX-2 pharmacophore was synthesized and evaluated for their COX-2 inhibitory activity. According to COX-1/COX-2 inhibition data, all compounds (6a-g) were selective inhibitors of COX-2 isoenzyme with IC values in the highly potent 0.08-0.

Design, synthesis, and biological evaluation of new pyrazino[1,2-a]benzimidazole derivatives as selective cyclooxygenase (COX-2) inhibitors.

A new class of pyrazino[1,2-a]benzimidazole derivatives possessing the SO Me pharmacophore at the para position of the C-3 phenyl ring was designed, synthesized, and tested for their cyclooxygenase-2 (COX-2) inhibitory, anti-cancer and anti-platelet aggregation activities. In vitro COX-1/COX-2 inhibition studies showed that 2-(4-methylphenyl)-1-methylene-3-(4-(methylsulfonyl)phenyl)-1,2-dihydropyrazino-[1,2-a]benzimidazole (5g) was the most potent COX-2 inhibitor (IC  = 0.08 μM) and 2-(3,4,5-trimethoxyphenyl)-1-methylene-3-(4-(methylsulfonyl)phenyl)-1,2-dihydropyrazino-[1,2-a]benzimidazole (5m) had the highest selectivity index (SI > 909).