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

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

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.

• Language: English
• Keywords: 3-Methyl-2-phenyl-1H-indole, antiproliferative activity, topoisomerase II, apoptosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: Str. 691-697
• Numbering: Vol. 11, iss. 5
• PID: 20.500.12556/RUL-141908
• UDC: 576.36: 615.4:54
• ISSN on article: 1948-5875
• DOI: 10.1021/acsmedchemlett.9b00557
• COBISS.SI-ID: 4874609
• Publication date in RUL: 11.10.2022

Record is a part of a journal

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

Secondary language

• Language: Slovenian
• Keywords: apoptoza, rak (medicina)

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208-2015
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: Other - Other funder or multiple funders
• Funding programme: Ministero dell’Istruzione, dell’Università e della Ricerca