Design, Synthesis and Biological Evaluation of New 4-(4-(Methylsulfonyl) Phenyl)-6-Phenylpyrimidin-2-Amine Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.

Introduction: Cyclooxygenase, an enzyme that occurs in at least two distinct variants (COX-1 and COX-2), is the target of classical inhibitors, which lack selectivity and inhibit both types of COX. However, a recent approach focuses explicitly on inhibiting COX-2, commonly found in inflamed tissue, resulting in fewer adverse effects than COX-1 inhibitors.

Methods: A series of 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine derivatives were synthesized through a two-step process.

Novel dual inhibitor targeting FAAH and sEH: Design, synthesis, and in-vitro evaluation of oxadiazole analogues.

Fatty acid amide hydrolase (FAAH) enzyme, as a potential therapeutic target for the treatment of pain and inflammation, is responsible for decomposing fatty acid amides like endocannabinoids. One attractive technique for increasing the efficacy of FAAH inhibitors is to generate antinociception and anti-inflammatory effects via another route, such as soluble epoxide hydrolase (sEH) inhibition, at the same time. In this study, two series of structures bearing oxadiazole rings as dual inhibitors of FAAH/sEH were designed, synthesized, and biologically evaluated.

Recent Advances in Therapeutic Potential of Dual-Acting Aromatase/COX-2.

Aromatase, a crucial enzyme assigned for transforming androgen into estrogen, has a vital function in the advancement of drug-resistant breast cancers that respond to endocrine treatments. Aromatase (CYP19A1) is a monooxygenase from the cytochrome P450 family that is involved in the conversion of androgens to estrogens. Breast cancer cells express aromatase activity, indicating that the tumor cells may be able to produce local estrogen.

Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review of Structure-Activity Relationship Studies.

Context: Dipeptidyl peptidase 4 (DPP-4) is a serine exopeptidase enzyme that hydrolyzes the amide bond at the N-terminal of peptides. This enzyme converts incretins, such as glucagon-like peptide I and glucose-dependent insulinotropic peptide, into their inactive forms, thereby preventing them from stimulating insulin secretion. Numerous studies have confirmed the role of DPP-4 in the pathophysiology of type 2 diabetes, leading to the development of various DPP-4 inhibitors.

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.

Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2.

Chalcones as Potential Cyclooxygenase-2 Inhibitors: A Review.

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.

Dual COX-2/15-LOX inhibitors: A new avenue in the prevention of cancer.

Dual cyclooxygenase 2/15-lipoxygenase inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 (cyclooxygenase-2) inhibitors for the treatment of inflammatory diseases, as well as preventing the cancer. Indeed, these latter present diverse side effects, which are reduced or absent in dual-acting agents. In this review, COX-2 and 15-LOX (15-lipoxygenase) pathways are first described in order to highlight the therapeutic interest of designing such compounds.

Effects of Extract Alone and Combined with Extract on Monosodium Iodoacetate Model of Osteoarthritis in Mice.

Background: As a chronic joint condition, osteoarthritis (OA) is a common problem among older people. Pain, aching, stiffness, swelling, decreased flexibility, reduced function, and disability are the symptoms of arthritis.

Objectives: In this study, we tested the extracts of (ZJE) and (BSE) to reduce OA symptoms as an alternative treatment.

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.

Attenuation of Inflammatory Responses in Breast and Ovarian Cancer Cells by a Novel Chalcone Derivative and Its Increased Potency by Curcumin.

Background: Breast and ovarian cancers are two common malignancies in women and a leading cause of death globally. The aim of the present study was to explore the effects of a novel chalcone derivative 1-(4-(methylsulfonyl)phenyl)-3-(phenylthio)-3-(p-tolyl)propane-1-one (MPP) individually or combined with curcumin, a well-known herbal medicine with anticancer properties, as a new combination therapy on inflammatory pathways in breast and ovarian cancer cell lines.

Methods: LPS-induced NF-B DNA-binding activity and the levels of proinflammatory cytokines were measured in the MPP- and MPP-curcumin combination-treated MDA-MB-231 and SKOV3 cells by ELISA-based methods.

Design, Synthesis, Docking Studies, Enzyme Inhibitory and Antiplatelet Aggregation Activities of New 1,3-Diphenyl-3-(Phenylthio)Propan-1-One Derivatives as Selective COX-2 Inhibitors.

Background: Cancer is the second leading cause of death worldwide after heart disease. A vast number of studies indicated that selective cyclooxygenase-2 (COX-2) inhibitors could be chemopreventive against different types of cancer because the expression of COX-2 is increased. Therefore, to develop new therapeutics for cancer, the design and synthesis of new COX-2 inhibitors with few side effects seem attractive as anti-cancer agents.

Design, Synthesis and Biological Evaluation of 1,3-Diphenyl-3-(phenylthio)propan-1-ones as New Cytotoxic Agents.

Cancers in terms of morbidity and mortality are one of the major universal issues. New compounds of anticancer agents based on β-aryl-β-mercapto ketones scaffold possessing piperidinylethoxy or morpholinylethoxy groups were synthesized and evaluated as cytotoxic agents. Cytotoxic effects of synthesized compounds were measured against MCF-7, human ER-positive breast cancer cell lines, using MTT assay.