Some morpholine tethered novel aurones: Design, synthesis, biological, kinetic and molecular docking studies.

Enzymes are the biological macromolecules that have emerged as an important drug target as their upregulation/imbalance leads to various pathological conditions, such as inflammation, parasitic infection, Alzheimer's, cancer, and many others. Here, we designed and synthesized some morpholine tethered novel aurones and evaluated them as potential inhibitors for CTSB, α-amylase, lipase and activator for trypsin. All the newly synthesized compounds were fully characterized by various spectroscopic techniques (1H NMR, 13C NMR, HRMS) and the Z-configuration to them was assigned based on single crystal XRD data and 1H NMR chemical shift values. Further, the hybrids were evaluated for their intracellular (cathepsin B) and extracellular (trypsin, lipase, amylase) enzyme inhibition potencies. The in-vitro inhibition screening against cathepsin B revealed that most of the synthesized compounds are good competitive inhibitors (% inhibition = 22.91-75.04), with 6q (% inhibition = 75.04) and 6r (% inhibition = 71.13) as the eminent inhibitors of the series. At the same time, they exhibited weak to moderate inhibition towards amylase (% inhibition = 7.22-22.48) and lipase (% inhibition = 16.29-54.83). A significant trypsin activation (% activation = 107.42-196.47) was observed even at the micromolar concentration of the compounds. Furthermore, the drug-modeling studies showed a good correlation between the in-vitro experimental results and the calculated binding affinity of the screened compounds with all the tested enzymes. These findings are expected to provide a new lead in drug development for different pathological disorders wherever these enzymes are involved.

A decennary update on diverse heterocycles and their intermediates as privileged scaffolds for cathepsin B inhibition.

The identification of x-ray crystal structure of cathepsin B (CTSB) in the early 90's enabled researchers to embark on a journey to understand and demystify its multiple catalytic mechanisms (endopeptidase/carboxypeptidase/peptidyl-dipeptidase) in diverse physiological processes and their switching into one another under different conditions. The engagement of CTSB in different pathological conditions due to its over-expression further highlighted the enhanced research interest around the domain. The occurrence of over-expressed CTSB in various diseases like Alzheimer's, cancer, arthritis, cardiovascular, etc., and the use of CTSB inhibitors for the treatment of these diseases have established its involvement in different pathological conditions. Such an understanding tempted researchers to design, synthesize, and screen diverse classes of compounds against CTSB. This in turn, helped in understanding their interactions with the active sites of the enzyme. Heterocyclic compounds comprise a very rich and broad class of medicinally important compounds that also hold great potential for CTSB inhibition. This review covers the CTSB inhibition potential of various natural and synthetic heterocyclic scaffolds. Researchers working in the fields of molecular modeling, drug design and development, and enzyme inhibitors can benefit significantly from this review.

A minireview of 1,2,3-triazole hybrids with O-heterocycles as leads in medicinal chemistry.

Over the past few decades, the dynamic progress in the synthesis and screening of heterocyclic compounds against various targets has made a significant contribution in the field of medicinal chemistry. Among the wide array of heterocyclic compounds, triazole moiety has attracted the attention of researchers owing to its vast therapeutic potential and easy preparation via copper and ruthenium-catalyzed azide-alkyne cycloaddition reactions. Triazole skeletons are found as major structural components in a different class of drugs possessing diverse pharmacological profiles including anti-cancer, anti-bacterial, anti-fungal, anti-viral, anti-oxidant, anti-inflammatory, anti-diabetic, anti-tubercular, and anti-depressant among various others. Furthermore, in the past few years, a significantly large number of triazole hybrids were synthesized with various heterocyclic moieties in order to gain the added advantage of the improved pharmacological profile, overcoming the multiple drug resistance and reduced toxicity from molecular hybridization. Among these synthesized triazole hybrids, many compounds are available commercially and used for treating different infections/disorders like tazobactam and cefatrizine as potent anti-bacterial agents while isavuconazole and ravuconazole as anti-fungal activities to name a few. In this review, we will summarize the biological activities of various 1,2,3-triazole hybrids with copious oxygen-containing heterocycles as lead compounds in medicinal chemistry. This review will be very helpful for researchers working in the field of molecular modeling, drug design and development, and medicinal chemistry.