An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called and, with an anti-proliferative effects, achieving IC values of about half that of the IC of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the and compounds induced cell cycle arrest in the G/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to .
Background:
Since the Monastrol discovery in 1999 as the first inhibitor of Eg5, functionalized
dihydropyrimidinones/thiones (DHPMs) have emerged as prototypes for drug design in different
targets. The present work aimed to evaluate the antifungal activity of a chemical library of DHPMs.
Methods:
The compounds were obtained employing Biginelli reaction. Their antifungal activities were
assessed against C. neoformans and C. albicans.
Results:
The compounds 1-i and 1-k inhibited moderately the fungal growth of C. neoformans, with
compound 2-k presenting MIC80 values of 62.5-125 µg·mL-1. Considering activity against C. albicans,
the compounds 1-i and 1-n present an MIC50 value of 125-250 µg·mL-1.
Conclusion:
The changes performed in DHPM scaffold appear to be valuable for generating compounds
with potential antifungal effect.
Doxazosin is an important drug used for treating hypertension and prostatic hyperplasia. An enantiomeric mixture (R)/(S) doxazosin mesylate was complete characterized by NMR and additionally FT-IR spectroscopy techniques. Were performed different NMR experiments, such as APT, HSQC, and HMBC in order to confirm the NMR signals assignments. All the hydrogens and the most of carbons atoms were assigned.
Nature often produces compounds with a high degree of symmetry to reduce structural information and complexity. Synthesis of identical twin drugs, through the linkage of two identical pharmacophoric entities, is a classical strategy to produce more potent and/or selective drugs. Herein, two units of the privileged core of the coumarin hymecromone were linked together using "click chemistry". Synthesis of 1-[2-(4-Methyl-7-coumarinyloxy)ethyl]-4-(5-{1-[2-(4-methyl-7-coumarinyloxy)ethyl]-1H-1,2,3-triazol-4-yl}pentyl)-1H-1,2,3-triazole was achieved by coupling of two identical units of an azido coumarin with a symmetrical alkine using copper(I)-catalyzed alkyne-azide cycloaddition reaction, in good yields and with complete regioselectivity.
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