title: 1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues-Model Compounds Targeting Oxidative Stress.
abstract: Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry.
authors.affiliation: Laboratory of Membrane Active Compounds and Beta-Diketones, Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
authors.forename: Astrida
authors.initials: A
authors.lastname: Velena
authors.affiliation: Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
authors.forename: Neven
authors.initials: N
authors.lastname: Zarkovic
authors.affiliation: Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.
authors.forename: Koraljka
authors.initials: K
authors.lastname: Gall Troselj
authors.affiliation: Laboratory of Membrane Active Compounds and Beta-Diketones, Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
authors.forename: Egils
authors.initials: E
authors.lastname: Bisenieks
authors.affiliation: Laboratory of Membrane Active Compounds and Beta-Diketones, Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
authors.forename: Aivars
authors.initials: A
authors.lastname: Krauze
authors.affiliation: Laboratory of Membrane Active Compounds and Beta-Diketones, Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Poikans
authors.affiliation: Laboratory of Membrane Active Compounds and Beta-Diketones, Latvian Institute of Organic Synthesis, Riga LV-1006, Latvia.
authors.forename: Gunars
authors.initials: G
authors.lastname: Duburs
mesh_terms: D017311:Amlodipine / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000737:chemistry; D002417:Cattle; D004095:Dihydropyridines / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry; D009578:Nitrobenzenes; D016877:Oxidants / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects*; D010879:Piperazines
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008077:Lipoproteins, LDL; D009578:Nitrobenzenes; D016877:Oxidants; D010879:Piperazines; C015145:dihydronicotinamide; D017311:Amlodipine; D009536:Niacinamide; C060285:lacidipine; C061004:benidipine; D001383:Azetidinecarboxylic Acid; C054218:manidipine; C038806:1,4-dihydropyridine; D006859:Hydrogen; D009543:Nifedipine; C061679:azelnidipine; C060343:lercanidipine