Effects of the Converting Enzyme Inhibitor Quinapril (CI-906) on Blood Pressure, Renin-Angiotensin System, and Prostanoids in Essential Hypertension

Säynävälammi, P; Pörsti, Ilkka; Pörsti, P; Nurmi, Anna-Kaisa; Seppälä, Erkki; Manninen, Vesa; Vapaatalo, Heikki

doi:10.1097/00005344-198807000-00012

Cited by 14 publications

(5 citation statements)

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“…As mentioned earlier, the isoquinoline and thieno[2,3‐b]pyridine motifs are widely common in approved drugs and drug candidates, (Alexopoulos, 2014; Ganellin & Elks, 2014; Gautam et al, 2022; Y. J. Kim et al, 2008; Prasad et al, 1973; Säynävälammi et al, 1988, p. 12; Sleebs et al, 2011; Wu et al, 2009) both have a pyridine ring in common. Upon employing a molecular merging strategy on both scaffolds (while preserving only one pyridine ring), thieno[2,3‐c]isoquinoline is produced (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…Alkaloids are important scaffolds in cancer chemotherapy (Kittakoop et al, 2013). Due to the popularity of isoquinoline (Ganellin & Elks, 2014; Gautam et al, 2022; Y. J. Kim et al, 2008; Prasad et al, 1973; Säynävälammi et al, 1988), thieno[2,3‐c]pyridine (Alexopoulos, 2014), and thieno[2,3‐b]pyridine/quinoline alkaloid scaffolds in medicinal chemistry (see Figure 1), a greater focus was placed on using these scaffolds as a basis for the development of novel HCC‐targeting chemotypes. Moreover, the thienoisoquinoline scaffold was considered in this study with special interest as a promising fused heterocyclic one newly introduced in cancer chemotherapy (see compounds IV and V [Figure 1] and the relevant discussion).…”

Section: Introductionmentioning

confidence: 99%

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Thieno[2,3‐c]isoquinolines: A novel chemotype of antiproliferative agents inducing cellular apoptosis while targeting the G2/M phase and Tubulin

Marae

Maklad

Samir

et al. 2023

Drug Development Research

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In the era of modern synthetic methodology and advanced bio‐evaluation techniques and considering the notorious history of hepatocellular carcinoma (HCC), hopeful expectations regarding novel bioactive chemotypes have grown dramatically. Among the widely versatile motifs in drug discovery studies are isoquinoline and thieno[2,3‐b]pyridine. Herein, the molecular merging of both motifs evoked thieno[2,3‐c]isoquinoline as a novel antiproliferative chemotype being hardly studied against HCC. Accordingly, compound series 4, 5, 7 and 8 were synthesized and bioevaluated against the HepG2 cell line. The role of C7‐Ac/C8‐OH substituents, C8‐C9 unsaturation, 1H‐pyrrol‐1‐yl ring closure at C1‐NH2 and C6‐Ph p‐halo‐substitution were biologically studied and successfully furnished the lead 5b while showing safe profile against Vero cells. Further, flow cytometric and Annexin V‐FITC/PI apoptotic bio‐investigations of 5b unveiled remarkable cell cycle arrest at the G2/M phase besides a 60‐fold increase in apoptosis. The use of a DFT conformational study followed by Molecular docking and molecular mechanics/generalized born surface area scoring evoked potential tubulin‐targeting activity of 5b at colchicine‐binding site, which was confirmed by experimental evidence (Tub Inhib IC50 = 71 µM vs. 14 µM for colchicine). Accordingly, preserving C7‐acetyl and optimizing halogen position while preserving [6S,7R]‐stereochemistry is crucial for optimum binding to colchicine binding site of tubulin.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thieno[2,3‐c]isoquinolines: A novel chemotype of antiproliferative agents inducing cellular apoptosis while targeting the G2/M phase and Tubulin

Marae

Maklad

Samir

et al. 2023

Drug Development Research

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“…However, specific mechanisms are not yet understood. Presumably, PM 2.5 accumulates in the gut microbiome ( Bäumler and Sperandio, 2016 ) to produce diseases such as inflammation, obesity, metabolic syndrome, diabetes mellitus, and carcinogenesis ( Säynävälammi et al, 1986 ).…”

Section: Pm Accumulation In Human Tissuesmentioning

confidence: 99%

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

Gavito-Covarrubias,

Ramírez-Díaz,

Guzmán-Linares

et al. 2024

Front. Genet.

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Environmental pollution nowadays has not only a direct correlation with human health changes but a direct social impact. Epidemiological studies have evidenced the increased damage to human health on a daily basis because of damage to the ecological niche. Rapid urban growth and industrialized societies importantly compromise air quality, which can be assessed by a notable accumulation of air pollutants in both the gas and the particle phases. Of them, particulate matter (PM) represents a highly complex mixture of organic and inorganic compounds of the most variable size, composition, and origin. PM being one of the most complex environmental pollutants, its accumulation also varies in a temporal and spatial manner, which challenges current analytical techniques used to investigate PM interactions. Nevertheless, the characterization of the chemical composition of PM is a reliable indicator of the composition of the atmosphere, the quality of breathed air in urbanized societies, industrial zones and consequently gives support for pertinent measures to avoid serious health damage. Epigenomic damage is one of the most promising biological mechanisms of air pollution-derived carcinogenesis. Therefore, this review aims to highlight the implication of PM exposure in diverse molecular mechanisms driving human diseases by altered epigenetic regulation. The presented findings in the context of pan-organic cancer, fibrosis, neurodegeneration and metabolic diseases may provide valuable insights into the toxicity effects of PM components at the epigenomic level and may serve as biomarkers of early detection for novel targeted therapies.

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“…The importance of the prostaglandins and particularly of vascular prostacyclin in the blood pressure-reducing action of the ACE inhibitors is especially demonstrated when these agents are administered simultaneously with indomethacin. 43) although the inhibition of ACE activity and the fall in blood pressure remained undiminished [226]. 42).…”

Section: Angiotensin I Converting Enzyme Inhibitorsmentioning

confidence: 99%

“…Influence of 12 weeks' treatment with quinapril on the activity of the angiotensin-converting enzyme (ACE), the diastolic blood pressure(RRd) and the concentration of the prostacyclin metabolite 6-oxo-PGFi " (PGF in) in the urine of patients with essential hypertension[226] conditions are quite reversed, and in this group the stimulating effect of the ACE inhibitors on the kinins and prostaglandins, especially vascular-formed prostacyclin, may share the responsibility for the blood pressure-reducing properties of this group of substances.…”

mentioning

confidence: 99%

Prostacyclin and Hypertension

Bönner¹,

Rahn²

1990

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Effects of the Converting Enzyme Inhibitor Quinapril (CI-906) on Blood Pressure, Renin-Angiotensin System, and Prostanoids in Essential Hypertension

Cited by 14 publications

References 0 publications

Thieno[2,3‐c]isoquinolines: A novel chemotype of antiproliferative agents inducing cellular apoptosis while targeting the G2/M phase and Tubulin

Thieno[2,3‐c]isoquinolines: A novel chemotype of antiproliferative agents inducing cellular apoptosis while targeting the G2/M phase and Tubulin

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

Prostacyclin and Hypertension

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