Structural Diversity and Mutational Challenges of Toll-Like Receptor 4 Antagonists as Inflammatory Pathway Blocker.

Toll-like receptor 4 (TLR4) is an important mediator that activates bacterial inflammation through its signaling pathway. It binds lipopolysaccharide (LPS) in the presence of myeloid differentiation protein 2 (MD2) to dimerise the TLR4-MD2-LPS complex. The TLR4 mediated signaling pathway stimulates cytokine production in humans, initiating inflammatory responses.

MD simulations for rational design of high-affinity HDAC4 inhibitors - Analysis of non-bonding interaction energies for building new compounds.

This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (HA3, 9F4, EBE, and TFG) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (HA3, 9F4, EBE) or diol (TFG) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation.

Novel aryl (dithioglycosyl)methane derivatives as anti-proliferative agents.

In a quest of developing carbohydrate derived anti-cancer agents, novel carbohydrate dithioacetal derivatives have been synthesized and evaluated for their potential as anti-proliferative agents against breast cancer cell lines (MCF-7 and MDA-MB-231) as well as non-cancerous kidney epithelial cell line (NKE). Total 18 compounds have been screened and 3 compounds showed promising anti-proliferative activities against cancer cells with low cytotoxicity to the normal cells using MTT assay. The mode of action of the best active compound has been proposed based on several microscopic studies.

Novel Sulforaphane Analog Disrupts Phosphatidylinositol-3-Kinase-Protein Kinase B Pathway and Inhibits Cancer Cell Progression via Reactive Oxygen Species-Mediated Caspase-Independent Apoptosis.

Sulforaphane, a naturally occurring isothiocyanate, has gained attention due to its tremendous anticancer potential. Thus, an array of sulforaphane analogs were synthesized and evaluated for their cytotoxic potentials on a wide range of malignant cell lines. Among these derivatives, compound displayed exceptional potency in inhibiting the proliferation of cancer cell lines and a negligible effect on normal cell lines through G2/M phase arrest.