Ronald P. Quintana

Relationships between the chemical constitution of carbamoylpiperidines and related compounds, and their inhibition of ADP-induced human blood platelet aggregation

Abstract The effect of a series of carbamoylpiperidines and related compounds on ADP-induced human blood platelet aggregation was studied. The systematic and gradual changes in the chemical structure of these synthetic entities disclosed highly significant relationships between molecular constitution, physicochemical properties and biodynamic effects, and yielded data suggesting -for the first time- platelet membrane inhibitory target sites spaced at 8 A. Inhibitory potencies culminated with a compound active at 5 μM concentrations; the latter and a number of other derivatives were much more effective than aspirin.

Effects of ethanol and of other factors on ADP-induced aggregation of human blood platelets in vitro

Abstract In studying the inhibition of ADP-induced human platelet aggregation, it became necessary to ascertain exacting conditions for interpreting biodynamic responses generated by even minor alterations in molecular constitution. The influence of ethanol was evaluated along with the effect of post-venipuncture and incubation time. The experimental conditions were studied in the absence as well as in the presence of platelet-aggregationinhibitor aspirin.

Surface-Chemical Studies on Chlorhexidine and Related Compounds: II. Interactions with Monomolecular-Film Systems

Interactions of chlorhexidine and structurally related biguanides with selected monomolecular-film systems (that is, stearic acid, stearyl alcohol, and N-octadecylacetamide) were explored. The data reflected the significance of ionic associations between the compounds and stearic acid films and, in the instance of the biguanide analogs, indicated that the length of the alkyl chain was an important factor in the penetration process.

Surface-Chemical Studies on Chlorhexidine and Related Compounds: 1. Effects at Air-Water, n-Hexane-Water, and Hydroxyapatite-Water Interfaces

The comparative ability of chlorhexidine diacetate and structurally related compounds to generate surface pressure at air-water and n-hexane-water interfaces, and to adsorb to hydroxyapatite, was determined. The order of effectiveness generally evident was 1-(p-chlorophenyl)-5-n-octylbiguanide acetate >> chlorhexidine diacetate ≥ 1-(p-chlorophenyl)-5-n-hexylbiguanide acetate > 1-(p-chlorophenyl )-5-n-propylbiguanide acetate > p-chlorophenylbiguanide acetate ~ p-chloro-phenylguanidine acetate.

Grisan derivatives in pure and mixed monomolecular films

Abstract Pressure-area isotherms for monolayers of two synthetic grisan derivatives have been determined and correlated with molecular orientations of these entities at the air-water interface. Isotherms for equimolar mixtures of the grisan derivatives with stearic acid, cholesterol, and l -α-lecithin, respectively, are reported. The pressure-area curves show, in general, the predominant influence of the grisan derivatives at low pressures, and ejection of these from the monolayer at intermediate pressure values. At higher pressures the curves reflect largely the properties of the respective lipids. Theoretical curves for the mixtures were calculated assuming additivity, and compared with the corresponding experimentally derived isotherms.

Surface activity and human blood platelet aggregation-inhibitory potency

Surface and interfacial activity is correlated with molecular constitution and inhibitory potency of mono- and bis(carbamoylpiperidino)alkanes and aralkanes, and of some corresponding quaternary pyridinium congeners, in ADP-induced human blood platelet aggregation. The measurements of surface and interfacial tension were carried out at concentrations and pH-values approximating those employed in the hemodynamic study. The effect of changes in chemical structure, ranging from relatively minor variations in a specific functional group to the alteration of major components in molecular constitution, was examined and interpreted in terms of contemporary theoretical chemistry.

Interaction of human blood platelet aggregation inhibitors with phospholipid films

Abstract A series of carbamoylpiperidines and related entities, a class of compounds only recently identified by the authors as potent human blood platelet aggregation inhibitors, showed correspondingly strong levels of “specific” interaction, in monomolecular film systems, with some phospholipids viewed as prototypes of actual platelet plasma membrane constituents. The data strongly corroborate our previously articulated view that our compounds possess appropriate hydrophobic character to penetrate the lipid bilayer of the platelet plasma membrane, subsequently are capable of generating sufficient quantities of their cationic species to counteract massively stimulus-induced mobilization of Ca ++ ions, and thereby restrain or void Ca ++ -dependent phospholipase activity.

Aspirin analogs with enhanced interfacial activity

Abstract A series of salicylic acid and acetylsalicylic acid analogs was synthesized, some of which possess impressively enhanced interfacial activity. The variance in the effect of these congeners on interfacial tension is interpreted in terms of their structural features and physicochemical properties.

Hexachlorophene esters in pure and mixed monomolecular films

Abstract The properties of pure monomolecular films of hexachlorophene monoundecanoate (I), hexachlorophene monostearate (II), and hexachlorophene diundecanoate (III) have been determined. The pressure-area curves for compounds I and II reflect a similar molecular orientation at the air-water interface for these compounds; films of each of the latter were considerably more stable than those of compound III and reflected the significance of the phenolic-OH function in the interaction with the subphase. Pressure-area isotherms for mixtures of compound I, as well as for those of compound II, with stearyl alcohol, stearic acid, methyl stearate, and stearyl acetate, respectively, showed positive deviations from the additivity rule; negative deviations were observed for mixtures of compound I, or of compound II, with tristearin. The data are indicative of interaction between component molecules in the respective films.

Prophylactic agents effecting lysis of dental plaque. Penetration of monomolecular films of stearyl alcohol and of N-octadecylacetamide by N-dodecylurea and related compounds

Abstract The effects of N-dodecylurea (I), dodecyl carbamate (II), myristamide (III), N-dodecylguanidine (IV), and N-dodecylthiourea (V) upon monomolecular films of stearyl alcohol and of N-octadecylacetamide were studied. The data reflect that compounds I and II elicit significant interactions associated with film-disruption.