Hemodynamic and Humoral Effects of Chronic Antihypertensive Treatment with Fenquizone: Importance of Aldosterone Response

Abstract

The effects of 1-year antihypertensive treatment with the diuretic fenquizone were evaluated in 16 patients with mild essential hypertension. During treatment with placebo, after 2, 4, 24, and 52 weeks of treatment we measured blood pressure, heart rate, forearm blood flow (FBF) and vascular resistance (FVR) at rest and after 10 minutes ischemia, and forearm venous distensibility. Subjects whose diastolic blood pressure after fenquizone was reduced at least 10% were classified as responders. On this basis, 56% of patients after 1 month and 68% after 1 year responded to fenquizone. Responders, in comparison to nonresponders, were characterized by a greater increase in FBF and a greater decrease in FVR. The reduction in diastolic blood pressure was significantly related to the fall in FVR whereas no correlation was found between blood pressure and venous compliance changes. Nonresponders had a PRA increase similar to that observed in responders but they showed a much greater increase in aldosterone, whose changes were inversely related to modifications of both FVR and blood pressure. Our results demonstrate that chronic therapy with fenquizone causes a reduction of FVR, and that nonresponders have an exaggerated rise in aldosterone. This observation further reinforces the hypothesis that factors influencing the secretion of aldosterone are important determinants of the antihypertensive mechanism of diuretics.

Treatment of cancer cells with chemotherapeutic drugs results in profound changes in expression of genes encoding aldehyde-metabolizing enzymes

“…Hyperproduction of ROS-generated carbonyls leads to transcriptional activation of genes encoding aldehyde-metabolizing enzymes, which belong to two major families of evolutionary conserved aldehyde scavengers: 1) aldehyde dehydrogenases (ALDHs) that catalyze the oxidation of aldehydes to carboxylic acids; and 2) aldo-keto reductases (AKRs), which reduce aldehydes to alcohols. It was shown that high expression levels of ALDHs and AKRs can protect cancer cells from the action of chemotherapeutic drugs 4, 5, as a consequence of either detoxification of ROS-generated toxic aldehydes or direct drug inactivation 6-8. Besides, AKRs increase survival rate of cancer cells by modulation of lipid biosynthesis and mitochondrial function 9.…”

2,3-Dihydroquinazolin-4(1H)-one as a privileged scaffold in drug design

“…282 Among them, fenquizone is a FDA-approved drug for the treatment of edema and hypertension. [283][284][285][286] The substitution of C8 with N in the benzene ring of DHQ and the introduction of 287 Some DHQ derivatives also show broad-spectrum antimicrobial properties. 2-(5-Nitro-2-thienyl) DHQs showed antibacterial activity against Hemophilus vaginalis and Escherichia coli strains, responsible for bacterial vaginitis, exhibiting low minimal inhibitory concentration (MIC, ranging from 0.4 to 12.5 mg ml À1 ).…”

Synthesis of tetrahydroquinazolines from 2-aminobenzonitriles and alkylidene malonates via 1,4-conjugate addition and an unprecedented rearrangement reaction

“…1). For instance, fenquizone (A) 2 is an FDA approved diuretic drug whereas DPC 083 (C) 3 exhibits HIV inhibitory activity. Quinethazone (B), 4 a thiazide diuretic, is commonly used for the treatment of hypertensive disorder and compound (E) 5 is a butyrylcholinesterase inhibitor.…”