TY  - JOUR
TI  - Further considerations to improve the druggability of biaryl hydroxy-triazole and fluorene-triazole hybrids
AU  - Liu, Zhiqi
AU  - Zhang, Meihong
AU  - Huang, Zhengwei
PY  - 2025
JO  - Exploration of Drug Science
VL  - 3
SP  - 1008134
DO  - 10.37349/eds.2025.1008134
UR  - https://www.explorationpub.com/Journals/eds/Article/1008134
AB  - Buarque et al. (Explor Drug Sci. 2025;3:1008107. DOI: 10.37349/eds.2025.1008107) reported the synthesis of 13 biaryl hydroxy-1,2,3-triazoles and 11 fluorene-1,2,3-triazole hybrids via optimized Suzuki and telescopic one-pot reactions. Cytotoxicity evaluations against colorectal cancer (HCT-116), astrocytoma (SNB-19), triple-negative breast cancer (MDA-MB-231), and acute myeloid leukemia, FLT3-ITD mutant (MOLM-13) cell lines revealed promising antitumor activity. 1-(2-bromophenyl)-4-(9H-filoren-9-yl)-1H-1,2,3-triazole (LSO258) and 1-(4-bromophenyl)-4-(2-fluoro-9H-fluron-9-yl)-1H-1,2,3-triazole (LSO272), both being fluorene-1,2,3-triazole hybrids with bromine substituents, could selectively inhibit the activity of MOLM-13 cells, while the biaryl hydroxy-1,2,3-triazoles compounds exhibited broader antitumor activity. It is worth noting that an inevitable phenomenon is observed: The above compounds have significant aromatic structural characteristics, and their large aromatic systems lead to increased molecular hydrophobicity, resulting in poor water solubility. This critical druggability limitation will directly restrict the development of formulations. To tackle this issue, this paper proposes micelles as the optimal solution. As a carrier structure formed by the self-assembly of amphiphilic surfactants, micelles possess a unique “hydrophobic core-hydrophilic shell” configuration. Their hydrophobic core layer can efficiently encapsulate triazole compounds containing aromatic structures. Compared to other nanomedicine formulations such as solid dispersions and nanoencapsulation technology, micelles demonstrate significant advantages in terms of stability, process simplicity, and biocompatibility.
ER  -