Correlation of biological activity and high-pressure liquid chromatographic retention index for a series of propranolol, barbiturate, and anthranilic acid analogs

Baker, John K.; Rauls, David O.; Borne, Ronald F.

doi:10.1021/jm00197a005

Cited by 43 publications

(10 citation statements)

References 5 publications

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“…Retention in HPLC has also been correlated directly with biological activity. 13,16,17 The HPLC methods possess all the advantages of the TLC methods plus the added advantages of accuracy, ease of controlling experimental conditions, and potential for automation. A broader range of lipophilicity can be analyzed by HPLC, and the development of chemically bonded reverse phases allows production of stable columns in which the contribution of the support to the chromatography can be minimized.…”

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confidence: 99%

A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity relationships

Brent¹,

Sabatka²,

Minick³

et al. 1983

J. Med. Chem.

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A highly deactivated octadecyl-bonded silica column and a mobile phase consisting of an water-methanol mixture in the range of blood pH and ionic strength are used to correlate log kappa' with biological activity for a series of sulfonamides and barbiturates. The results were compared to literature methods by using retention volume (VR) and retention indexes (I). For the nine sulfonamides tested, log VR and log kappa' were used with and without correction for ionization. For each biological end point (protein binding and minimum inhibitor concentration against Eschericia coli from two sources) and each independent variable (log kappa' and log VR) the residual standard derivation for the regression was determined. the standard derivations were compared in an F test for each of 12 relevant regressions. Log kappa' was statistically superior in for cases, while log VR was superior in one case. Overall, the methods were statistically indistinguishable. Log kappa' values and I values for 15 barbiturates were regressed against three biological end points [hypnotic activity (the minimum effective dose in rabbits), inhibition of Arbacia egg cell division, and inhibition of rat brain respiration]. Standard deviations were compared by an F test, and the two methods were indistinguishable as far as the goodness of biological correlations are concerned. Procedures for controlling the column's activity are presented. Choices for an appropriate mobile phase are discussed, and a method of calculating pH and ionic strength in a methanol-aqueous mobile phase is presented.

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mentioning

confidence: 99%

A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity relationships

Brent¹,

Sabatka²,

Minick³

et al. 1983

J. Med. Chem.

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“…Baker er al. (27), proposed that the ordered side chains and residual silanol groups of untreated octadecylsilane packing material best reflects a biolayer, and partition data obtained from such systems are more suitable for use in biological correlations. A commercially available untreated reverse-phase packing material was used throughout our experimental procedure.…”

Section: Resultsmentioning

confidence: 99%

Liquid Chromatographic Determination of Lipophilicity with Application to a HomologousSeries of Barbiturates

Toon

Mayer²,

Rowland³

1984

Journal of Pharmaceutical Sciences

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“…The n-octanol/water partition coefficient (kow), determined by the traditional shake-flash method, is the parameter most commonly reported as a measure of the lipophilic character of chemicals, although frequently an insufficient kow data set is a problem in structure-activity relationship studies. The correlation between the capacity factor (k') obtained from RP-HPLC methods and kow is generally accepted for simple and rapid es-timation of partition coefficients [34] [35] [36] [37]. With this in mind, we established RP-HPLC as alternative method to evaluate the lipophilicity of the indole series.…”

Section: Structure-activity Relationshipmentioning

confidence: 99%

Chemical Basis for the Phytotoxicity of Indoles in Relation to the Allelopathy of Cereals

Bravo¹,

Copaja²

2018

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Phytotoxic activity of an indole series substituted with electron-acceptor and electron-donor groups in the aromatic ring was determined. They are potential decomposition products, of natural indole alkaloids in cereals plants with allelopathic properties. Phytotoxic selectivity was evaluated from antialgal activity against the microalga Chlorella vulgaris, seed germination seeds and biomass weight of seedling of barley, rye, wheat, oat and maize species and the weed Lolium rigidum. Lipophilia character of the compounds was determined by RP-HPLC method. Both, the electronic character of the substituents, evaluated from σ p parameter, and the lipophilia character of the molecules measured from logP HPLC parameter, are involved in the phytotoxic activity. The three bio indicators has shown that the compounds with the higher electron-acceptor groups showed the higher level of phytotoxicity and the molecules with electron-donor groups showed the lowest activity, although, in some cases, this behavior is modified by the lipophilic properties of the molecules. These results are rationalized in terms of polarization of N-H bond of heterocyclic ring. Compounds with the higher logP HPLC values showed the higher phytotoxic activity. Further evidence on the role of lipophilicity was obtained from linear regression between the average inhibitions percentages of biomass and logP HPLC values. The activity increased linearly by increasing the lipophilic character of the compounds. Therefore, quantitative effects in the phytotoxic activity of the electronic properties of the substituents in the aromatic ring and lipophilic character of the indoles can be inferred from σ p and logP HPLC parameters, respectively. The results strongly suggest that the potential decomposition products of the natural indole alkaloids from cereals or other natural sources may be in connection with the allelopathic phenomenon of plants when are released into the soil.

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Correlation of biological activity and high-pressure liquid chromatographic retention index for a series of propranolol, barbiturate, and anthranilic acid analogs

Cited by 43 publications

References 5 publications

A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity relationships

A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity relationships

Liquid Chromatographic Determination of Lipophilicity with Application to a HomologousSeries of Barbiturates

Chemical Basis for the Phytotoxicity of Indoles in Relation to the Allelopathy of Cereals

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