Thermal, X-ray Structural, and Dissolution Characteristics of Solid Forms Derived from the Anticancer Agents 2-Methoxyestradiol and 2-Methoxyestradiol-3,17-O,O-Bis-Sulfamate

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

“…In each case, kneading an equimolar physical mixture of the respective host and 2ME produced an amorphous phase, as evidenced by a PXRD pattern devoid of peaks characteristic of the crystalline component 2ME. Consistent with this, no melting endotherm for 2ME was observed in DSC traces of these preparations, whereas the traces of the corresponding CD-2ME physical mixtures revealed fusion of 2ME at a peak temperature of 188 °C (reported mp 187 °C [ 9 ]). Definitive inclusion complex formation between 2ME and both of the host molecules was finally confirmed by comparing the FTIR spectrum of pure 2ME with those of the pure CD and the putative CD-2ME inclusion complexes prepared by kneading; characteristic bands for 2ME (at 1600, 2861, 2903, 3179 and 3413 cm −1 ) were seen to either undergo significant shifts or be masked by broad bands of the hosts RAMEB and HPBCD in the spectra of the materials prepared by kneading.…”

“…(A graphical overlay of the molecules appears in the Supporting Information File 1 ). Thus, in the DIMEB inclusion complex, the steroid skeleton retains the same conformation as that recently observed in the crystal of 2ME, as well as in crystals of the solvated phase 2ME·(CHCl 3 ) 2 and the sulfamoylated derivative of 2ME, namely 2-methoxyestradiol-3,17-di, O -bis-sulfamate [ 9 ], the A-ring being planar (aromatic), the B-, C- and D-rings being a half-chair, a chair and a twist form (twisted on C13–C14) respectively. Thus, no significant distortions of the host or guest conformations are evident as a result of inclusion of the 2ME molecule in the host DIMEB.…”

“…Comparison of the conformation of the encapsulated 2ME molecule and that of the same molecule in its own crystal structure [ 9 ] shows that there is minimal difference, with a RMSD of only 0.084 Å and a maximum deviation between two equivalent atoms of 0.202 Å. (A graphical overlay of the molecules appears in the Supporting Information File 1 ).…”

“…Although recent reports of ongoing clinical trials with 2ME continue to appear [ 6 – 7 ], attention has shifted towards its more promising derivatives, such as 2-methoxyestradiol-3,17-di, O -bis-sulfamate (2MES), with higher potency and improved pharmacokinetic properties [ 8 ]. Nevertheless, as noted in our recent report on some aspects of the solid-state chemistry of 2ME and 2MES [ 9 ] several new indications for 2ME in the area of anticancer therapy, in particular, coupled with the well-established low toxicity of underivatised 2ME, have revived interest in this compound [ 9 – 10 ], providing ongoing motivation for increasing its poor bioavailability.…”

New organotin(IV) chlorides derived from N-(2-hydroxyphenyl)aryloxy sulfamates. Synthesis, characterization and DSC investigation

“…Sulfamates are found to be suitable intermediates for the design and development of various types of new molecules as therapeutic agents and for biological or pharmaceutical uses. Sulfamate derivatives have been identified as bioactive molecules which occupy a prominent place in medicinal chemistry because of their wide range therapeutic properties, such as anti-cancer, [1][2][3][4][5] antibacterial, [6][7][8][9][10] antioxidant, 11,12 anti-HIV, [13][14][15] anticonvulsant, [16][17][18][19] antibiotic, 13,20,21 antiobesity, 22 diuretic, 23,24 hypoglycemic, 25 antithyroid, 26 and anti-neuropathic pain 27 activities. In addition, the electronic structure of −SO 2 NH 2 group in sulfamates and related ligands was considered as moiety par excellence for designing potent carbonic anhydrases inhibitors (CAIs) because of its good chelating to the metal ion of the enzyme.…”