Sunitinib (Sun) is a widely used anticarcinogen in the treatment of renal cell carcinoma and gastrointestinal stromal tumors. Nevertheless, the suboptimal solubility and hygroscopic nature of the commercial Sun malate (Sum), coupled with the array of toxic side effects associated with chronic and high-dose therapy, significantly constrain its treatment compliance and therapeutic potential. Hence, to enhance solubility and attempt to achieve a therapeutic outcome that reduces toxicity and enhances efficacy, this study introduces dicarboxylic acids with varying chain lengths to synthesize seven salts. The structural analyses indicate that the introduction of coformer has led to significant changes in the charge distribution of the electrostatic potential on the surface of the Sun molecule, thereby altering its polarity, intermolecular interactions, and solubility. Further analysis on interaction energies and conformations demonstrates that within the Sun molecule, the electron-rich rigid conjugated segment tends to maximize overlap to form pi-stacking interactions, while the flexible segment compromises to enhance the overall thermodynamic stability of the compound. Unexpectedly, SunPA (propanedioic acid) exhibits not only favorable solubility and low hygroscopicity but also promising antitumor activity, suggesting its promising prospects for further development. Building on these findings, this research not only promotes our understanding of the role of introducing suitable coformers in regulating properties of Sun but also provides enlightenment for the development of insoluble alkaline and semiflexible active pharmaceutical ingredients, in order to better potentially improve their therapeutic effect and stability.
Humanity's global footprint now far exceeds Earth's capacity to renew resources and absorb waste. Recent studies show that several ecological thresholds have been surpassed, some of which experts have deemed critical. Six of the nine safe planetary boundaries, as specified in Steffen et al (2015), have already been breached, leading to unprecedented biodiversity collapse, resource depletion, and increased climate risk. Staying within a "safe operating space" is crucial to prevent an irreversible environmental change (Rockström et al 2009). In practice, however, many large-scale developmental activities go unchecked, while ignoring the enormous stresses on water, soils, nutrients, and species. To address this urgent unmet need, we propose an Earth Credits Framework (ECF): a unified accounting system that quantifies a project's total planetary consumption, integrates the existing carbon credit system, and establishes a limit on the number of Earth Credits that can be justifiably allocated within the nine planetary boundaries. With sufficient data and accepted standards, ECF can offer governments, funders, and agencies a reliable compass for investing in truly sustainable outcomes.
Biotechnology and BioengineeringVolume 117, Issue 6 p. 1603-1606 ISSUE INFORMATIONFree Access Biotechnology and Bioengineering: Volume 117, Number 6, June 2020 First published: 08 May 2020 https://doi.org/10.1002/bit.27047AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume117, Issue6June 2020Pages 1603-1606 RelatedInformation
