benzofurans and khellinone

Previous and recent scientific research has shown that triazolopyrimidine and furochromones have a wide range of pharmacological activities for the treatment of numerous diseases, including anticancer, antiviral, anti-depressant, anti-microbial, anti-inflammatory, and analgesic activities.. Preparation of new drugs derived from a natural furochromones as (1-hydrazinyl or methylthio),-furopyrimidoquinazolinone, 1, 2, 4-triazolopyrimidofuroquinazolin-5-one, and quinazoline- pyrimidofuro- quinazoline-8, 10-dione and the study of their biological activity as antimicrobial agents.. A series of novel N'-furopyrimidoquinazoline-hydrazide; 1, 2, 4-triazolopyrimidofuroquinazolin- 5-one; furopyrimidoquinazolin-3-one and quinazoline-pyrimidofuroquinazoline-8, 10- dione derivatives were synthesized from substituted (methylthio)-furopyrimidoquinazolinone (3ab) and 1-hydrazinyl-furopyrimido- quinazolinone (4a-b) as the starting material.. All compounds were synthesized in good yields (71-95%) in a gradually efficient system under mild condition and some of the procedures were used such as microwave oven. The new compounds have been confirmed by means of different spectroscopic methods such as IR, 1D and 2D -NMR techniques and mass spectrum. The in vitro antimicrobial activities were evaluated for the prepared compounds using many types of bacteria (Gram-positive and Gram-negative) and fungi.. 1, 2, 4-triazolopyrimidofuroquinazolin-5-one derivatives (10a-f, 8a-b, 7a-b and 6a-d) showed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.

Topics: Anti-Infective Agents; Benzofurans; Chemistry Techniques, Synthetic; Microbial Sensitivity Tests; Quinazolinones; Structure-Activity Relationship

Substituted-6-methyl-1-thioxo-1,2-dihydro-3

Topics: Anti-Infective Agents; Benzofurans; Chemistry Techniques, Synthetic; Microbial Sensitivity Tests; Molecular Structure; Quinazolinones

A quantitative-structure activity relationship (QSAR) study has been made on two different series of sodium channel blockers--namely, a series of 3-(4-phenoxyphenyl)pyrazoles and a series of 2-alkyl-4-arylimidazoles--and a series of potassium channel blockers that comprises of khellinone derivatives, which act on voltage-gated K(+) channels Kv1.3. In both the cases--the inhibition of Na+ channels or the inhibition of K+ channels--the significant correlations were obtained between the inhibition potencies and the hydrophobic properties of the compounds. This led to suggest that the hydrophobic property of the compounds is a major determining factor of the Na+/K+ channel blocking activity and that the compounds might elicit their effects through the hydrophobic interactions with the receptors.

Topics: Benzofurans; Cell Line; Humans; Imidazoles; Potassium Channel Blockers; Pyrazoles; Quantitative Structure-Activity Relationship; Regression Analysis; Sodium Channel Blockers

Chalcone derivatives of the natural product khellinone were synthesised and screened for bioactivity against the voltage-gated potassium channel Kv1.3. X-ray crystallography was employed to investigate relationships between the structure and function of a selection of the reported chalcones.

Topics: Benzofurans; Chalcones; Crystallography, X-Ray; Electrophysiology; Humans; Kv1.3 Potassium Channel; Models, Chemical; Molecular Structure; Potassium Channel Blockers; Structure-Activity Relationship

The voltage-gated potassium channel Kv1.3 constitutes an attractive target for the selective suppression of effector memory T cells in autoimmune diseases. We have previously reported the natural product khellinone, 1a, as a versatile lead molecule and identified two new classes of Kv1.3 blockers: (i) chalcone derivatives of khellinone, and (ii) khellinone dimers linked through the 6-position. Here we describe the multiple parallel synthesis of a new class of khellinone derivatives selectively alkylated at either the 4- or 7-position via the phenolic OH and show that several chloro, bromo, methoxy, and nitro substituted benzyl derivatives inhibit Kv1.3 with submicromolar potencies. Representative examples of the most potent compounds from each subclass, 11m (5-acetyl-4-(4'-chloro)benzyloxy-6-hydroxy-7-methoxybenzofuran) and 14m (5-acetyl-7-(4'-bromo)benzyloxy-6-hydroxy-4-methoxybenzofuran), block Kv1.3 with EC50 values of 480 and 400 nM, respectively. Both compounds exhibit moderate selectivity over other Kv1-family channels and HERG, are not cytotoxic, and suppress human T cell proliferation at low micromolar concentrations.

Topics: Benzofurans; Cell Line; Cell Proliferation; Humans; Immunosuppressive Agents; In Vitro Techniques; Kv1.3 Potassium Channel; Patch-Clamp Techniques; Potassium Channel Blockers; Structure-Activity Relationship; T-Lymphocytes