Design, synthesis, and antitumor efficacy of novel 5-deazaflavin derivatives backed by kinase screening, docking, and ADME studies

• Main Authors: Walaa A. Bedewy (Author), Mosaad S. Mohamed (Author), Ahmed M. Abdelhameed (Author), Mohamed A. Elsawy (Author), Mohammed Al-Muhur (Author), Noriyuki Ashida (Author), Ashraf N Abdalla (Author), Tamer A. Elwaie (Author), Tomohisa Nagamatsu (Author), Hamed I. Ali (Author)
• Format: Book
• Published: Taylor & Francis Group, 2023-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Novel 5-deazaflavins were designed as potential anticancer candidates. Compounds 4j, 4k, 5b, 5i, and 9f demonstrated high cytotoxicity against MCF-7 cell line with IC50 of 0.5-190nM. Compounds 8c and 9g showed preferential activity against Hela cells (IC50: 1.69 and 1.52 μM respectively). However, compound 5d showed notable potency against MCF-7 and Hela cell lines of 0.1 nM and 1.26 μM respectively. Kinase profiling for 4e showed the highest inhibition against a 20 kinase panel. Additionally, ADME prediction studies exhibited that compounds 4j, 5d, 5f, and 9f have drug-likeness criteria to be considered promising antitumor agents deserving of further investigation. SAR study showed that substitutions with 2-benzylidene hydra zino have a better fitting into PTK with enhanced antiproliferative potency. Noteworthy, the incorporation of hydrazino or ethanolamine moieties at position 2 along with small alkyl or phenyl at N-10, respectively revealed an extraordinary potency against MCF-7 cells with IC50 values in the nanomolar range.

Item Description

10.1080/14756366.2023.2220570
1475-6374
1475-6366