Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

Autor: Abd El-Rahman YA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt., Chen PJ; Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, 824410, Taiwan.; Graduate Institute of Medicine, I-Shou University, Kaohsiung, 824410, Taiwan., ElHady AK; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt.; School of Life & Medical Sciences, University of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt., Chen SH; School of Nursing, Fooyin University, Kaohsiung, 831301, Taiwan., Lin HC; Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung, 824410, Taiwan., El-Gamil DS; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt.; Department of Chemistry, Faculty of Pharmacy, Ahram Canadian University, Cairo, 12451, Egypt., Aboushady Y; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt., Abadi AH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt., Engel M; Pharmaceutical & Medicinal Chemistry, Saarland University, Campus C2.3, D-66123, Saarbrücken, Germany., Abdel-Halim M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
Jazyk: angličtina
Zdroj: Future medicinal chemistry [Future Med Chem] 2024; Vol. 16 (12), pp. 1239-1254. Date of Electronic Publication: 2024 May 22.
DOI: 10.1080/17568919.2024.2342708
Abstrakt: Aim: Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. Methods & results: We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound 16b , featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low IC 50 values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. It induced G2/M cell cycle arrest, apoptosis and inhibited cell migration by modulating apoptotic markers. Conclusion: 16b represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.
Databáze: MEDLINE