TY - DATA T1 - Subnanomolar indazole-5-carboxamide inhibitors of monoamine oxidase B (MAO-B) continued: indications of iron binding, experimental evidence for optimised solubility and brain penetration PY - 2017/07/20 AU - Nikolay T. Tzvetkov AU - Liudmil Antonov UR - https://tandf.figshare.com/articles/journal_contribution/Subnanomolar_indazole-5-carboxamide_inhibitors_of_monoamine_oxidase_B_MAO-B_continued_indications_of_iron_binding_experimental_evidence_for_optimised_solubility_and_brain_penetration/5226160 DO - 10.6084/m9.figshare.5226160.v1 L4 - https://ndownloader.figshare.com/files/8925949 KW - Alzheimer’s disease KW - free energy calculations KW - iron chelators KW - MAO inhibitors KW - Parkinson’s disease N2 - Pharmacological and physicochemical studies of N-unsubstituted indazole-5-carboxamides (subclass I) and their structurally optimised N1-methylated analogues (subclass II), initially developed as drug and radioligand candidates for the treatment and diagnosis of Parkinson’s disease (PD), are presented. The compounds are highly brain permeable, selective, reversible, and competitive monoamine oxidase B (MAO-B) inhibitors with improved water-solubility and subnanomolar potency (pIC50 >8.8). Using a well-validated, combined X-ray/modelling technology platform, we performed a semi-quantitative analysis of the binding modes of all compounds and investigated the role of the indazole N1 position for their MAO-B inhibitory activity. Moreover, compounds NTZ-1006, 1032, and 1441 were investigated for their ability to bind Fe2+ and Fe3+ ions using UV-visible spectroscopy. ER -