A click chemistry-based biorthogonal approach for the detection and identification of protein lysine malonylation for osteoarthritis research.

Lysine malonylation is a post-translational modification where a malonyl group, characterized by a negatively charged carboxylate, is covalently attached to the Ɛ-amino side chain of lysine, influencing protein structure and function. Our laboratory identified Mak upregulation in cartilage under aging and obesity, contributing to osteoarthritis (OA). Current antibody-based detection methods face limitations in identifying Mak targets.

Facile synthesis of corticiolic acid-a bioactive pharmacophore from natural sources.

Fungal strains have inspired us to find the untapped sources of secondary metabolites. Corticiolic acid (CA, 2,4-dihydroxy-6-pentadecylbenzoic acid; from fungus, ) is one of the core active scaffolds in natural compounds such as Aquastatin-A, B, & C. CA can also be isolated from the plant .

Zn(II)-Curcumin Complexes-Based Anticancer Agents.

There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents.

Pyrrole: A Decisive Scaffold for the Development of Therapeutic Agents and Structure-Activity Relationship.

An overview of pyrroles as distinct scaffolds with therapeutic potential and the significance of pyrrole derivatives for drug development are provided in this article. It lists instances of naturally occurring pyrrole-containing compounds and describes the sources of pyrroles in nature, including plants and microbes. It also explains the many conventional and modern synthetic methods used to produce pyrroles.

In situ global proteomics profiling of EGCG targets using a cell-permeable and Click-able bioorthogonal probe.

Despite possessing a wide spectrum of biological activities, molecular targets of EGCG remain elusive and as a result, its precise mode of action is still unknown. Herein, we have developed a novel cell-permeable and Click-able bioorthogonal probe for EGCG, YnEGCG for in situ detection and identification of its interacting proteins. The strategic structural modification on YnEGCG allowed it to retain innate biological activities of EGCG (IC 59.

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry.

Chalcones are a class of privileged scaffolds with high medicinal significance due to the presence of an α,β-unsaturated ketone functionality. Numerous functional modifications of chalcones have been reported, along with their pharmacological behavior. The present review aims to summarize the structures from natural sources, synthesis methods, biological characteristics against infectious and non-infectious diseases, and uses of chalcones over the past decade, and their structure-activity relationship studies are detailed in depth.

Design, synthesis and bioactive properties of a class of macrocycles with tunable functional groups and ring size.

The design and synthesis of a versatile class of macrocycles with tunable functional groups and ring size are unfolded. Herein, a synthetic strategy is reported to furnish a new class of macrocycles in multi-gram scale in a two-step reaction. The total time taken for synthesizing a macrocycle is 1.

Nuclear factor-κB plays an important role in Tamarixetin-mediated inhibition of matrix metalloproteinase-9 expression.

Flavonoids possess a broad spectrum of pharmacological properties, including anti-cancer, anti-oxidant and immunomodulatory activities. The current study explored the potential of some less-studied flavonoids in inhibiting Matrix Metalloproteinase-9 (MMP-9), a prominent biomarker, upregulated in a variety of cancers and known to promote migration and invasion of cancer cells. Amongst these, Tamarixetin, a naturally occurring flavonoid derivative of Quercetin, demonstrated significant dose-dependent inhibition of MMP-9 expression.

(I-3,II-3)-Biacacetin-mediated cell death involves mitochondria.

Dysregulation of the dynamic balance between cell proliferation and cell death leads to several malignancies including cancer. Biflavones are known to possess anti-proliferative activity against numerous cancer cell lines. The current study was undertaken to understand the mechanism of action of the biflavonoid (I-3,II-3)-biacacetin on MDA-MB-231.

6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition.

An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation.

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone.

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells.

Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor.

Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a diverse range of therapeutic applications including cardio-protection, there have been no reports on the effect of AA on CA II. The present study describes for the first time, the novel zinc independent inhibition of CA II by AA.

Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9.

Eleven biflavones (7a-b and 9a-i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor. Molecular docking studies suggest that unlike most of the known inhibitors, 9h inhibits MMP-2 and MMP-9 through non-zinc binding interactions.

Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells--A SAR study.

Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells.

Anacardic acid inhibits the catalytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9.

Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells.