التفاصيل البيبلوغرافية
| العنوان: |
Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes. |
| المؤلفون: |
Lanfranco, Alberto1 (AUTHOR), Rakhshan, Sahar1,2 (AUTHOR), Alberti, Diego2 (AUTHOR), Renzi, Polyssena1 (AUTHOR), Zarechian, Ayda2 (AUTHOR), Protti, Nicoletta3,4 (AUTHOR), Altieri, Saverio3,4 (AUTHOR), Crich, Simonetta Geninatti1,2 (AUTHOR) simonetta.geninatti@unito.it, Deagostino, Annamaria1 (AUTHOR) annamaria.deagostino@unito.it |
| المصدر: |
European Journal of Medicinal Chemistry. Apr2024, Vol. 270, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*CYCLODEXTRIN derivatives, *CARBONIC anhydrase, *BORON-neutron capture therapy, *CARBORANES, *MESOTHELIOMA, *IN vivo studies |
| الشركة/الكيان: |
HEWLETT-Packard Development Co. LP |
| مستخلص: |
Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer. [Display omitted] • The compounds were designed and prepared as multivalent agents for BNCT (Boron Neutron Capture Therapy) and the inhibition of carbonic anhydrase, including a carborane, a sulfamido functionality, and ureido moiety for a good selectivity. • In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). • In vitro BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation after irradiation. • In vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of CA IX inhibition combined with BNCT. • CA-USFs were administered as inclusion complexes of β-CD and CD polymers, in order to maximise the boron uptake and their in vivo tolerance at a therapeutic dose. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
