Investigation into improving the aqueous solubility of the thieno[2,3-b]pyridine anti-proliferative agents

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Zafar, Ayesha and Pilkington, Lisa I. and Haverkate, Natalie A. and Van Rensburg, Michelle and Leung, Euphemia and Kumara, Sisira and Denny, William A. and Barker, David and Alsuraifi, Ali and Hoskins, Clare and Reynisson, Jóhannes (2018) Investigation into improving the aqueous solubility of the thieno[2,3-b]pyridine anti-proliferative agents. Molecules, 23 (1). 145. ISSN 1420-3049 (https://doi.org/10.3390/molecules23010145)

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Abstract

It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H-pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by three orders of magnitude, from 1.2 µg/mL (1-thieno[2,3-b]pyridine) to 1.3 mg/mL (3-pyrrolo[2,3-b]pyridine), however, it was only marginally active against cancer cells. The second strategy involved loading a very potent thieno[2,3-b]pyridine derivative (2) into a cholesteryl-poly(allylamine) polymer matrix for water solubilisation. Suppression of human pancreatic adenocarcinoma (BxPC-3) viability was observed to an IC50 value of 0.5 μg/mL (1.30 μM) in conjunction with the polymer, which is a five-fold (×5) increase in potency as compared to the free drug alone, demonstrating the utility of this formulation approach.

ORCID iDs

Zafar, Ayesha, Pilkington, Lisa I., Haverkate, Natalie A., Van Rensburg, Michelle, Leung, Euphemia, Kumara, Sisira, Denny, William A., Barker, David, Alsuraifi, Ali, Hoskins, Clare ORCID logoORCID: https://orcid.org/0000-0002-7200-0566 and Reynisson, Jóhannes;
  • Item type:Article
    ID code:70517
    Dates:
    Date
    Event
    11 January 2018
    Published
    8 January 2018
    Accepted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:14 Nov 2019 12:58
    Last modified:11 Nov 2024 12:30
    URI:https://strathprints.strath.ac.uk/id/eprint/70517
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