Correlation of serum binding of penicillins with partition coefficients

Bird, A. E.; Marshall, A.C.

doi:10.1016/0006-2952(67)90215-8

Cited by 118 publications

(36 citation statements)

References 26 publications

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“…Moreover, the compound presents the highest value for the distributive parameter p, which is considered as the parameter of choice for correlating both binding to biological macromolecules and transport through a biological system [25][26][27][28] . The cytotoxic potency of 5 is probably affected by these descriptors, which can be important parameters for the interaction of 5 with the active sites of topoisomerase(s).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides

Siwek

Bielawska²,

Maciorkowska³

et al. 2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of eight thiosemicarbazide derivatives was examined for cytotoxicity in breast cancer cell cultures. Among them, 4-benzoylthiosemicarbazides proved to be only slightly less potent than chlorambucil in both MDA-MB-231 and MCF-7 lines. In contrast, 4-aryl/ alkylthiosemicarbazides revealed significantly lower cytotoxicity effect. Subsequently, all titled compounds were tested as potential human topoisomerase I and II (topo I and topo II) inhibitors. Mechanistic studies revealed that tested thiosemicarbazides act as both topoisomerase I and topoisomerase II inhibitors. Among them, the best inhibitory activity was found for 4-benzoylthiosemicarbazides (1 and 2) with IC 50 at 50 mM against topo II.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides

Siwek

Bielawska²,

Maciorkowska³

et al. 2013

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Bird and Marshall (2) showed that the binding of a series of penicillin analogs correlates with their partition coefficients and, thus, the hydrophobic nature of the molecules. The degree of protein binding increases as the side group confers a more hydrophobic nature on the molecule.…”

Section: Methodsmentioning

confidence: 99%

Simple spectrophotometric assay for measuring protein binding of penem antibiotics to human serum

Gootz

Subashi

Lindner

1988

Antimicrob Agents Chemother

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The binding of antibiotics to plasma (serum) proteins through hydrogen bonding can significantly influence the biological characteristics of these drugs. A rapid spectrophotometric assay has been developed that measures the level of free (unbound) penem antibiotic in serum ultrafiltrates. Whole human serum was adjusted to a standard concentration of antibiotic and then filtered by centrifugation through a Centrifree (Amicon Corp., Lexington, Mass.) filter that retained >99.9% of serum protein. The degree of penem protein binding was determined spectrophotometrically by measuring the level of unbound drug in the ultrafiltrate at 322 nm. At this wavelength, no interfering absorption from residual protein was detected in the ultrafiltrate, and penem absorption was linear over a wide concentration range. The method gave protein-binding values comparable to those obtained by a high-pressure liquid chromatography assay but was more rapid, since it did not require solvent extraction and high-pressure liquid chromatography calibration procedures. The spectrophotometric assay has been used to assay over 100 penems to determine the structure-activity relationships that are involved with the high serum protein binding of these agents. As with penicillins and some cephalosporins, the nonpolar nature of the penem side chain at the C-2 position strongly influenced the degree of penem binding to serum proteins.

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“…einer seiner Metabolite die Binduügsverhältnisse eines änderen Pharmakons ändern, zur Klärung des Mechanismus der von uns in Tierversuchen untersuchten Interaktion (1-5) beitragen. Die Literaturfülle der letzten zehn Jahre auf dem Gebiet der Bestimmung des freien Anteils eines Pharmakons in biologischem Material bietet hinsichtlich der angewandten Methoden ein einheitliches Bild: Benutzt wurden a) Gelfiltration (6-12) b) Gleichgewichtsdialyse (l 2-21) c) Ultrafiltration/-zentnfugation (12,(22)(23)(24)(25)(26)(27)(28)(29)(30) Ohne hier näher auf die Vor-und Nachteile der Gelund Ultrafiltration bzw. Ultrazentrifugation einzugehen (12), soll mit der vorliegenden Arbeit gezeigt werden, wie der wichtigste Nachteil der Gleichgewichtsdialyse, nämlich die Überlänge der Versuchsdauer (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) .…”

Section: Introductionunclassified

Untersuchung der Wechselwirkung von Carbamazepin und Promazin mit Rinderserumalbumin mit Hilfe einer neuen Dialysevorrichtung

Kinawi¹,

Teller²

1978

Clinical Chemistry and Laboratory Medicine

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Zusammenfassung: Der Aufbau und die Arbeitsweise einer neuen Dialysiervorrichtung werden beschrieben. Die Brauchbarkeit dieser Vorrichtung, die die Bestimmung des freien Anteils eines Pharmakons in einer AlbuminPharmakon-Pufferlösung bereits nach 10-15 Minuten ermöglicht, wurde hier durch die Ermittlung des freien Anteils von Carbamazepin bzw. Promazin in Albumin-Pufferlösungen demonstriert. Die hierbei erzielten Ergebnisse zeigten eine gute Übereinstimmung mit denen der Kontrollmethoden (Gleichgewichtsdialyse und Gelfiltration). Weiterhin wurde die Carbamazepin-Albumin-Bindung durch Ermittlung der Gesamtbindungskonstante (Ki), der scheinbaren (apparenten) Bindungskonstante (k + ), der Anzahl der Bindungsstellen/Albuminmolekül (n), der freien Reaktionsenergie AF° sowie des freien Anteils charakterisiert.

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Correlation of serum binding of penicillins with partition coefficients

Cited by 118 publications

References 26 publications

Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides

Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides

Simple spectrophotometric assay for measuring protein binding of penem antibiotics to human serum

Untersuchung der Wechselwirkung von Carbamazepin und Promazin mit Rinderserumalbumin mit Hilfe einer neuen Dialysevorrichtung

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