Disease relevance of cyclopropane

• A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis [1].
• Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto- and hydroxy-mycolic acids [2].
• At the N-1 position, a cyclopropyl group appears to be most potent with respect to minimal inhibitory concentrations against Enterobacteriaceae and Pseudomonas [3].
• Iso and anteiso C15:0 and C17:0 along with C18:0 were predominant in Gram-positive bacteria, while C16:1, C16:0, C18:1, and cyclopropyl cyC17:0 and cyC19:0 were significant in Gram-negative bacteria [4].
• Synthesis and antiviral activity of novel acyclic nucleosides: discovery of a cyclopropyl nucleoside with potent inhibitory activity against herpesviruses [5].

High impact information on cyclopropane

• For the compounds with an intact cyclopropyl group, the order of cytotoxic and mutagenic potency (molar basis) in V79 cells generally correlated with binding to calf thymus DNA, and increased with the length of the B segment [6].
• Plants and certain protists use cycloeucalenol cycloisomerase (EC ) to convert pentacyclic cyclopropyl sterols to conventional tetracyclic sterols [7].
• Highly stereoselective prins cyclization of silylmethyl-substituted cyclopropyl carbinols to 2,4,6-trisubstituted tetrahydropyrans [8].
• Incubation of 2b with PB microsomes resulted in p-hydroxylation and N-demethylation only; no loss or ring-opening of the cyclopropyl group occurred [9].
• N-dealkylation of an N-cyclopropylamine by horseradish peroxidase. Fate of the cyclopropyl group [10].

Chemical compound and disease context of cyclopropane

• Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency [11].
• The potential antitumor activity of a series of novel cyclopropyl compounds, which lack estrogen agonist activity, was evaluated in estrogen receptor positive human breast cancer cells (MCF-7) in culture [12].
• These data show that in broad terms the cytotoxic potency of bisamidines 1-3 in the cultured breast cancer MCF-7 cells decreases with the size of the alkyl group substituent (cyclopropyl > isopropyl > cyclopentyl), in accord with their increases in DNA affinity, as shown by the binding constant values [13].
• Analog II (1,1-dichloro-cis-2,3-diaryl cyclopropane) is a cyclopropyl compound which produces pure antiestrogenic activity in mice and inhibits the proliferation of breast cancer cells [14].
• Using the gas chromatography-mass spectrometry (GC-MS) method we found in Streptomyces cinnamonensis saturated fatty acids of iso- and anteiso- types, cyclopropyl acids, and unsaturated fatty acids where the double bond position was determined by MS of their pyrrolidine derivatives [15].

Biological context of cyclopropane

• Other cyclizations of alkynes with furans or electron-rich arenes give products of apparent Friedel-Crafts-type reactions, although these processes could also proceed by pathways involving the formation of cyclopropyl platinum carbenes [16].
• It has been postulated that metabolism via hydrogenation of the 8,9-double bonds of these molecules would unmask the electrophilic, and thus, the toxic nature of their cyclopropyl moieties [17].
• Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes [18].
• The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and N1 (ethyl, cyclopropyl, difluorophenyl) was also studied [19].
• Hydrolysis rates in aqueous buffered solution do not differ significantly in the allyl- and cyclopropyl series [20].

Anatomical context of cyclopropane

• This fatty acid, containing a cyclopropyl moiety in the beta,gamma-position, was designed to enter the myocardium by the same mechanism as natural fatty acids and to undergo partial metabolism before being trapped in the cell [21].
• Its structure is unique in that it contains the sequential positioning of a thiazoline and cyclopropyl ring, and it exerts its potent cell toxicity through interaction with the colchicine drug binding site on microtubules [22].
• These are the first reported cyclopropyl-containing fatty acid derivatives from a Lyngbya sp. Grenadadiene (1) has an interesting profile of cytotoxicity in the NCI 60 cell line assay, while grenadamide (2) exhibited modest brine shrimp toxicity (LD50 = 5 microg/mL) and cannabinoid receptor binding activity (Ki = 4.7 microM) [23].

Associations of cyclopropane with other chemical compounds

• Modifications favorable for binding affinity are (1). a thiomethyl group at C21 of the thiazole side chain, (2). a methyl group at C12 in S configuration, (3). a pyridine side chain with C15 in S configuration, and (4). a cyclopropyl moiety between C12 and C13 [24].
• Since the cyclopropyl ketone derivative 14 (ciproxifan) had high affinity in vitro as well as high potency in vivo, it was selected for further studies in monkeys [25].
• Reaction of enol ethers with alkynes catalyzed by transition metals: 5-exo-dig versus 6-endo-dig cyclizations via cyclopropyl platinum or gold carbene complexes [26].
• The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and the N-1 cyclopropyl substituents are desirable structural features in targeting M. tuberculosis gyrase [27].
• To clarify the structure-activity relationship of the sugar moiety, various 3'-C-carbon-substituted analogues, such as 1-propynyl, 1-butynyl, ethenyl, ethyl, and cyclopropyl derivatives, of ECyd and EUrd were synthesized [28].

Gene context of cyclopropane

• These results indicate that the relative configuration of the cyclopropyl ring in the L-arginine analogues significantly affects their inhibitory potential and NOS isoform selectivity [29].
• Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings [30].
• In this paper, we describe the characterization of the novel cyclopropyl-substituted product analogue 4'-phospho-N-(1-mercaptomethyl-cyclopropyl)-pantothenamide (PPanDeltaSH) as a mechanism-based inhibitor of the human PPC-DC enzyme [31].
• Enantioselective binding of an 11-cis-locked cyclopropyl retinal. The conformation of retinal in bovine rhodopsin [32].
• These values show that the tert-butyl substituent is at least as good as cyclopropyl in rendering high levels of antimycobacterial activity [33].

Analytical, diagnostic and therapeutic context of cyclopropane

• This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats [34].
• Monitoring by HPLC, the azaCBI ligand in the Co(III)(cyclen)(azaCBI) complex (2) slowly hydrolysed in aqueous solution, in contrast to the free ligand 1 which readily converted to its reactive cyclopropyl form [35].
• Gas chromatography coupled to mass spectrometry analyses of methanolyzed lipidic extracts from tissues incubated with each probe revealed that all the cyclopropyl fatty acids were transformed into the corresponding 11-cyclopropylidene acids, except for compound trans-5 (5b), which was not desaturated at C11 [36].
• The molecular structures of the 2-bromo-3-cyclopropyl-1-phosphapropene, 1,2-bis(cyclopropyl)-3,4-diphosphinidenecyclobutene and the digold complex were unambiguously determined by X-ray crystallography and are discussed from the point of view of the cyclopropyl conjugation [37].

References