Synthesis, antiproliferative effect and topoisomerase II inhibitory activity of 3-methyl-2-phenyl-1H-indoles

Zidar, Nace (avtor), Secci, Daniela (avtor), Tomašič, Tihomir (avtor), Peterlin-Mašič, Lucija (avtor), Kikelj, Danijel (avtor), Passarella, Daniele (avtor), Argaez, Aida Nelly Garcia (avtor), Hyeraci, Mariafrancesca (avtor), Via Dalla, Lisa (avtor)

A series of 3-methyl-2-phenyl-1H-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI50 values of the most potent compounds (32 and 33) were lower than 5 [micro]M in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition. The most potent derivative, 32, was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1H-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.

• Jezik: Angleški jezik
• Ključne besede: 3-Methyl-2-phenyl-1H-indole, antiproliferative activity, topoisomerase II, apoptosis
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: Str. 691-697
• Številčenje: Vol. 11, iss. 5
• PID: 20.500.12556/RUL-141908
• UDK: 576.36: 615.4:54
• ISSN pri članku: 1948-5875
• DOI: 10.1021/acsmedchemlett.9b00557
• COBISS.SI-ID: 4874609
• Datum objave v RUL: 11.10.2022

Gradivo je del revije

• Naslov: ACS medicinal chemistry letters
• Založnik: American Chemical Society
• ISSN: 1948-5875
• COBISS.SI-ID: 2959217

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: apoptoza, rak (medicina)

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208-2015
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Ministero dell’Istruzione, dell’Università e della Ricerca