Synthesis and in vitro cytotoxicity of benzoxazole-based PPARα/γ antagonists in colorectal cancer cell lines.

Autor: Moreno-Rodríguez N; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain., Laghezza A; Department of Pharmacy-Drug Science, University of Bari 'Aldo Moro', Bari, Italy., Cerchia C; 'Drug Discovery' Laboratory, Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Sokolova DV; Research, Institute of Experimental Therapy and Diagnostics of Tumor, NN Blokhin National Medical Center of Oncology, Moscow, Russia.; Department of Biochemistry, Patrice Lumumba Peoples' Friendship University, Moscow, Russia., Spirina TS; Research, Institute of Experimental Therapy and Diagnostics of Tumor, NN Blokhin National Medical Center of Oncology, Moscow, Russia.; Department of Biochemistry, Patrice Lumumba Peoples' Friendship University, Moscow, Russia., De Filippis B; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Romanelli V; 'Drug Discovery' Laboratory, Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Recio R; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain., Fernández I; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain., Loiodice F; Department of Pharmacy-Drug Science, University of Bari 'Aldo Moro', Bari, Italy., Pokrovsky VS; Research, Institute of Experimental Therapy and Diagnostics of Tumor, NN Blokhin National Medical Center of Oncology, Moscow, Russia.; Department of Biochemistry, Patrice Lumumba Peoples' Friendship University, Moscow, Russia., Ammazzalorso A; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Lavecchia A; 'Drug Discovery' Laboratory, Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Sep; Vol. 357 (9), pp. e2400086. Date of Electronic Publication: 2024 May 28.
DOI: 10.1002/ardp.202400086
Abstrakt: A series of benzoxazole-based amides and sulfonamides were synthesized and evaluated for their human peroxisome proliferator-activated receptor (PPAR)α and PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based on transactivation results, seven compounds were selected to test their in vitro antiproliferative activity in a panel of eight cancer cell lines with different expression rates of PPARα and PPARγ. 3f was identified as the most cytotoxic compound, with higher potency in the colorectal cancer cell lines HT-29 and HCT116. Compound 3f induced a concentration-dependent activation of caspases and cell-cycle arrest in both colorectal cancer models. Docking experiments were also performed to shed light on the putative binding mode of this novel class of dual PPARα/γ antagonists.
(© 2024 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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