Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling
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Pierre Redelinghuys
Abstract
Inhibition of angiotensin I-converting enzyme (ACE) has become an effective strategy in the treatment of hypertension and cardiovascular disease. Keto-ACE, a previously described C-domain selective ACE inhibitor, was used as the basis for the design, synthesis and molecular modelling of a series of novel ketomethylene derivatives for which ACE inhibition profiles and structural characterisation are reported. Ki determinations indicated that the introduction of a bulky aromatic tryptophan at the P2′ position of keto-ACE significantly increased selectivity for the C-domain, while an aliphatic P2 Boc group conferred N-domain selectivity. These data were supported by the potential energies of the compounds docked with the C- and N-domains of ACE.
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- Highlight: chronic oxidative stress and cancer
- Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
- Does Helicobacter pylori cause gastric cancer via oxidative stress?
- Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis
- Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
- Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
- Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells
- Evidence for attenuated cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine removal in cancer patients
- The roles of ATP in the dynamics of the actin filaments of the cytoskeleton
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- A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms
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- Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue
- BID, an interaction partner of protein kinase CK2α
- Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity
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