A novel thiazole-sulfonamide hybrid molecule as a promising dual tubulin/carbonic anhydrase IX inhibitor with anticancer activity
Khasawneh, Hussam Elddin Nabeih; Ali, Elryah I.; Elmagzoub, Ranya Mohammed ; Al-Aouadi, Raed Fanoukh Aboqader; Almagharbeh, Wesam Taher; Alotaibi, Ghallab; Bräse, Stefan
1,2; Alkhammash, Abdullah
1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)
2 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
1,2; Alkhammash, Abdullah1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)
2 Institut für Organische Chemie (IOC), Karlsruher Institut für Technologie (KIT)
Abstract:
Introduction:
Multitargeted anticancer agents can overcome resistance by
simultaneously modulating key pathways. This study reports a novel thiazole -
chalcone/sulfonamide hybrid (compound 7) designed to inhibit both tubulin
polymerization and carbonic anhydrase IX (CA IX).
Methods:
Compound 7 was synthesized through a five-step sequence and
characterized by NMR and elemental analysis. Its cytotoxicity was assessed
against cancer (HT-29, A549, 786-O, MCF-7) and normal (WI-38) cell lines.
Tubulin polymerization and CA isoform inhibition (I, II, IX, XII) were evaluated.
Apoptosis induction was confirmed by measuring p53, Bax, Bcl-2, and caspases 3
and 9. Molecular docking, ADMET, and DFT studies supported
mechanistic insights.
Results and discussion:
Compound 7 showed potent activity against HT-29 cells
(IC 50 = 0.98 μM) and low toxicity toward WI-38 cells. It inhibited tubulin
polymerization (IC 50 = 2.72 μM) and selectively targeted CA IX (IC 50 = 0.021
μM) and CA XII, while sparing CA I and II. Apoptotic effects were confirmed by
increased p53 and Bax, reduced Bcl-2, and activation of caspases. Docking
studies revealed key interactions within the colchicine-binding site of tubulin
... mehr
Multitargeted anticancer agents can overcome resistance by
simultaneously modulating key pathways. This study reports a novel thiazole -
chalcone/sulfonamide hybrid (compound 7) designed to inhibit both tubulin
polymerization and carbonic anhydrase IX (CA IX).
Methods:
Compound 7 was synthesized through a five-step sequence and
characterized by NMR and elemental analysis. Its cytotoxicity was assessed
against cancer (HT-29, A549, 786-O, MCF-7) and normal (WI-38) cell lines.
Tubulin polymerization and CA isoform inhibition (I, II, IX, XII) were evaluated.
Apoptosis induction was confirmed by measuring p53, Bax, Bcl-2, and caspases 3
and 9. Molecular docking, ADMET, and DFT studies supported
mechanistic insights.
Results and discussion:
Compound 7 showed potent activity against HT-29 cells
(IC 50 = 0.98 μM) and low toxicity toward WI-38 cells. It inhibited tubulin
polymerization (IC 50 = 2.72 μM) and selectively targeted CA IX (IC 50 = 0.021
μM) and CA XII, while sparing CA I and II. Apoptotic effects were confirmed by
increased p53 and Bax, reduced Bcl-2, and activation of caspases. Docking
studies revealed key interactions within the colchicine-binding site of tubulin
... mehr
| Zugehörige Institution(en) am KIT | Institut für Biologische und Chemische Systeme (IBCS) Institut für Organische Chemie (IOC) |
| Publikationstyp | Zeitschriftenaufsatz |
| Publikationsjahr | 2025 |
| Sprache | Englisch |
| Identifikator | ISSN: 2296-2646 KITopen-ID: 1000183349 |
| HGF-Programm | 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems |
| Erschienen in | Frontiers in Chemistry |
| Verlag | Frontiers Media SA |
| Band | 13 |
| Seiten | Art.-Nr.: 1606848 |
| Vorab online veröffentlicht am | 26.06.2025 |
| Nachgewiesen in | Dimensions OpenAlex Web of Science Scopus |
| Globale Ziele für nachhaltige Entwicklung |