Exploring target selectivity in designing and identifying PI3Kα inhibitors for triple negative breast cancer with fragment-based and bioisosteric replacement approach.

Triple-negative breast cancer (TNBC) is one of the most fatal malignancies in the world, accounting for 42% of all deaths due to metastasis. The significant development is hindered by the multi-drug resistance and poor patient compliance. PIK3CA gene mutation is one of the important causes of TNBC, which causes dysregulation of the cell cycle and cell proliferation.

A Structure-Based Design Strategy with Pyrazole-Pyridine Derivatives Targeting TNFα as Anti-Inflammatory Agents: E-Pharmacophore, Dynamic Simulation, Synthesis and In Vitro Evaluation.

Any pathogenic attack, infection, or disease can initiate inflammation. It results in significant adverse consequences like inflammatory bowel disease, rheumatoid arthritis, etc. TNFα is one of the major pro-inflammatory cytokines for the progression of inflammation-the present study designed a series of hybrid compounds consisting of the pyrazole-pyridine moiety.

Computational-guided approach for identification of PI3K alpha inhibitor in the treatment of hepatocellular carcinoma by virtual screening and water map analysis.

Hepatocellular carcinoma (HCC) is one of the most deadly disorders, with a relative survival rate of 36% in the last 5 years. After an extensive literature survey and pathophysiology analysis, PI3Kα was found to be a promising biological target as PIK3CA gene upregulation was observed in HCC, resulting in the loss of apoptosis of cells, which leads to uncontrollable growth and proliferation. Due to superior selectivity and promising therapeutic activity, the PI3K-targeted molecule library was selected, and the ligand preparation was executed.

Identification of natural product as selective PI3Kα inhibitor against NSCLC: multi-ligand pharmacophore modeling, molecular docking, ADME, DFT, and MD simulations.

Non-small cell lung cancer (NSCLC) is a widespread and often aggressive form of cancer affecting people worldwide. PIK3CA missense mutations play a significant role in the progression of growth factor signaling in cancer, making PI3Kα an important biological target for inhibition against NSCLC. Natural product molecules with PI3Kα inhibitory activity are promising therapeutic agents for the treatment of NSCLC, owing to their selectivity and potentially lower toxicity compared to synthetic compounds.

Calixarenes and their Relevance in Anticancer Drug Development.

Calixarenes have always captured the attention of several researchers. They have the ability to entrap multiple molecules and form inclusion complexes with drugs due to their unique structure. Due to this property, they are being widely used in the development of several classes of drugs, most notably anticancer drugs.

Role of multi-targeted bioactive natural molecules and their derivatives in the treatment of Alzheimer's disease: an insight into structure-activity relationship.

Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses due to other unaltered physiological factors. The solution for this problem is Multi-targeted Drugs (MTDs), which can affect multiple determinants to realize the multifunctional effects. Acetylcholinesterase (AChE) inhibitors donepezil, rivastigmine, galantamine, and N-methyl-D-aspartate (NMDA) receptor antagonist memantine are FDA-approved drugs used to treat AD symptomatically.

Molecular docking and dynamics based approach for the identification of kinase inhibitors targeting PI3Kα against non-small cell lung cancer: a computational study.

Non-small cell lung cancer (NSCLC) is an obscure disease whose incidence is increasing worldwide day by day, and PI3Kα is one of the major targets for cell proliferation due to the mutation. Since PI3K is a class of kinase enzyme, and no research has been performed on the inhibition of PI3Kα mutation by small molecules, we have selected the protein kinase inhibitor database and performed the energy minimization process by ligand preparation. The key objective of this research is to identify the potential hits from the protein kinase inhibitor library and further to perform lead optimization by a molecular docking and dynamics approach.