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

in Future medicinal chemistry by Yara A Abd El-Rahman, Po-Jen Chen, Ahmed K ElHady, Shun-Hua Chen, Hsin-Chieh Lin, Dalia S El-Gamil, Youssef Aboushady, Ashraf H Abadi, Matthias Engel, Mohammad Abdel-Halim

TLDR

  • The study is about finding new ways to fight cancer. The researchers found that a type of medicine called multi-target kinase inhibitors can be very effective against cancer cells. They tested different types of these medicines and found that one of them, called compound, was very good at stopping the growth of cancer cells. The compound did this by stopping a group of proteins that cancer cells use to grow. The researchers think that compound could be a good lead for making new medicines that can fight cancer in many ways at once.

Abstract

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.We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound, featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low ICvalues 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.represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.

Overview

  • The study focuses on the development of multi-target kinase inhibitors to combat chemoresistance in cancer. The hypothesis being tested is that these inhibitors can effectively target multiple cancer-relevant kinases simultaneously and show significant anti-cancer effects. The methodology used for the experiment includes the screening of 5-hydroxybenzothiophene derivatives as potential multi-target kinase inhibitors, followed by the identification of a potent inhibitor with low IC values against key kinases. The primary objective of the study is to identify a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core. The study aims to answer the question of whether multi-target kinase inhibitors can effectively target multiple cancer-relevant kinases and show significant anti-cancer effects.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions, specifically the screening of 5-hydroxybenzothiophene derivatives as potential multi-target kinase inhibitors. The results show that compound featuring a 5-hydroxybenzothiophene hydrazide scaffold emerged as a potent inhibitor, displaying low IC values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. The compound induced G2/M cell cycle arrest, apoptosis, and inhibited cell migration by modulating apoptotic markers. The key findings of the study support the hypothesis that multi-target kinase inhibitors can effectively target multiple cancer-relevant kinases and show significant anti-cancer effects.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they suggest that multi-target kinase inhibitors can be an effective therapeutic strategy for combating chemoresistance in cancer. The study identifies a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core. However, the study also has limitations that need to be addressed in future research, such as the need for further preclinical and clinical studies to evaluate the safety and efficacy of the identified compound. Future research directions could include the development of new multi-target kinase inhibitors with improved potency and selectivity, as well as the exploration of the potential of these inhibitors in combination with other anti-cancer therapies.
Read Full Article