Characterization and Antiproliferative Activity of a Novel 2-Aminothiophene Derivative-β-Cyclodextrin Binary System

Abstract

The novel 2-aminothiophene derivative 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN) has shown potential anti-proliferative activity in human cancer cell lines. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop binary 6CN-β-cyclodextrin (βCD) systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. The 6CN-βCD binary systems were prepared by physical mixing, kneading and rotary evaporation methods and further characterized by FTIR, XRD, DSC, TG and SEM. In addition, molecular modeling and phase solubility studies were performed. Finally, MTT assays were performed to investigate the cytostatic and anti-proliferative effects of 6CN-βCD binary systems. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the aforementioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The MTT assay demonstrated the cytostatic and anti-proliferative activities of 6CN-βCD binary systems and therefore, these might be considered as promising candidates for new anticancer drugs.

β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

“…The TG/DTG curves of β-CD showed a mass loss event between 30–170 °C (13.57% ∆m1) attributed to the loss of water molecules from the β-CD cavity, and another event with a significant and rapid mass loss between 280–400 °C (73.15% ∆m3) due to the degradation of β-CD. Similar mass loss events for β-CD were reported previously [ 20 , 23 , 26 ].…”

Preparation and Physicochemical Evaluation of Lumefantrine-2-Hydroxypropyl-β-cyclodextrin Binary Systems

“…whereas in cases when the values are greater than 5000 , the drug/CD complexes are very strong and stable, which result in a partial release of the drug from the cavity [34][35][36]. Thus, the lumefantrine-2-HP-β-CD is expected to have a superior bioavailability profile compared to pure lumefantrine.…”

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

“…This particular structure of CDs confers them multiple applications in the pharmaceutical field, food, cosmetics, textile, and chemistry industry based on their property of forming guest–host inclusion complexes [ 6 , 7 , 8 , 9 , 10 ]. The inclusion complexation leads to an increase in the solubility of insoluble drug substances, including the antiviral drug remdesivir [ 11 ] to improve the chemical stability, the biological activity, and the bioavailability of guest molecules, to prevent drug–excipient or drug–drug interactions, to reduce/eliminate the unpleasant taste or odors and also ocular and gastrointestinal irritation [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Therefore, the encapsulation of the drug in the CD cavity results in a remarkable improvement of physicochemical, biopharmaceutical properties, and therapeutic potential of the guest [ 23 , 24 , 25 ].…”