Design, synthesis, in silico and in vitro evaluation of pyrrole-indole hybrids as dual tubulin and aromatase inhibitors with potent anticancer activities
1
Issued Date
2025-06-27
Resource Type
eISSN
20462069
Scopus ID
2-s2.0-105009375192
Journal Title
Rsc Advances
Volume
15
Issue
27
Start Page
21962
End Page
21976
Rights Holder(s)
SCOPUS
Bibliographic Citation
Rsc Advances Vol.15 No.27 (2025) , 21962-21976
Suggested Citation
Saruengkhanphasit R., Chatwichien J., Ngiwsara L., Lirdprapamongkol K., Niwetmarin W., Eurtivong C., Kittakoop P., Svasti J., Ruchirawat S. Design, synthesis, in silico and in vitro evaluation of pyrrole-indole hybrids as dual tubulin and aromatase inhibitors with potent anticancer activities. Rsc Advances Vol.15 No.27 (2025) , 21962-21976. 21976. doi:10.1039/d4ra09000d Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111105
Title
Design, synthesis, in silico and in vitro evaluation of pyrrole-indole hybrids as dual tubulin and aromatase inhibitors with potent anticancer activities
Corresponding Author(s)
Other Contributor(s)
Abstract
Twenty-four new pyrrolyl-3-phenyl-1H-indole-2-carbohydrazide derivatives were designed, synthesized and evaluated for their anticancer activities and dual inhibition properties against tubulin and aromatase. Their anticancer activities were highly potent against the NCI60 human cancer cell line panel. Amongst them, single chloro-substituted derivative 3h was the strongest tubulin inhibitor, disrupting the microtubule structure by inhibiting the colchicine site, while potently inhibiting aromatase (IC<inf>50</inf> = 1.8 µM) with strong activity against the estrogen receptor-positive T47D breast cancer cell line (IC<inf>50</inf> = 2.4 µM). Ester derivative 3k showed the best aromatase inhibitory activity (IC<inf>50</inf> = 18 nM) with moderate anti-T47D activity (IC<inf>50</inf> = 10.6 µM). Molecular docking predicted the derivatives inhibited the colchicine site of tubulin by forming mainly hydrophobic interactions with the surrounding amino acid residues. Moreover, heme chelation with the pyrrole ring was predicted as a key interaction, and the formation of intermolecular bonds with adjacent amino acid residues was predicted as important for inhibitory activity.