The histamine H4 receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H4R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H4R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H4R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.

The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.

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Aims: To investigates the stability of ATZ along with PIP under different stress conditions and characterization of degradants by LC-QTOF-ESI-MS including in-vitro cellular anticancer activity, in-vivo pharmacokinetics, and biodistribution studies. Background:: Anastrozole (ATZ) is being widely used in the treatment of breast cancer and it requires a high dose while long-term medication. ATZ high dose may kill the non-cancerous cells also and leads towards multidrug resistance (MDR) due to efflux of P-Glycoprotein. ATZ is reported for poor water solubility and lesser oral bioavailability. Piperine (PIP) has been reported to enhance the various pharmacokinetic parameters like bioavailability of various active pharmaceutical ingredients and phytoconstituents. PIP is known to inhibit drug transporter P-glycoprotein. PIP stops drug metabolism by inhibiting the action of P450/CYP3A4. Objective: To explore the stability studies of ATZ along with PIP in different stress conditions. it was also proposed to perform the characterization of degradants by LC-QTOF-ESI-MS including in-vitro cellular anticancer activity, in-vivo pharmacokinetics, and biodistribution studies. Method: Degradants were identified for molecular weight using LC-QTOF-ESI-MS and structures of degradants were confirmed by fragmentation pattern along with mass accuracy measurements. Pharmacokinetic and biodistribution were performed using Wistar rat and calculated Pharmacokinetic parameters for ATZ, PIP, and their combination. The validated method was used for stressed studies as well as bioanalytical. Result: A total of fourteen degradants were characterized. ATZ and PIP have shown synergistic anticancer effects in the 4T1 cell line and shown superior Pharmacokinetic and biodistribution with good oral absorption and high bioavailability. Conclusion: Therefore, there is huge scope in the future to conduct pharmacological and formulation studies for this combination.

Alzheimer's disease (AD), a progressive neurodegenerative disorder is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine via inhibiting acetylcholinesterase (AChE). The present study involves identification of newer AChE inhibitors by dual approach of e-pharmacophore and structure-based virtual screening of Asinex library. Robustness of docking protocol was validated by enrichment calculation with ROC value .71 and BEDROC value .028. Among 11 selected hits, ZINC72338524 with best MM-GBSA dG binding shows optimal range of CNS properties and ligand-AChE complex stability. Further, molecular dynamics study revealed its molecular interactions with Trp86, Phe338, and Tyr341 amino acid residues of catalytic anionic site and Tyr124, Ser125, and Trp286 amino acid residues of peripheral anionic site. Physicochemical properties and ADMET risk prediction indicates their potential in druggability and safety.