Abstract

Our main goal was to design and synthesize novel lomefloxacin derivatives that inhibit the topoisomerase II enzyme, leading to potent anticancer activity. Lomefloxacin derivatives substituted at position 3 and 7 were synthesized and screened for cytotoxic activity utilizing 60 different human cancer cell lines. Furthermore, compounds 3a,b,c,e that revealed potent broad-spectrum anticancer activity (with mean percent GI more than 47%) were further evaluated using five dose concentrations and calculating the GI50. Compound 3e was then evaluated for cell cycle analysis and demonstrated cell cycle arrest at the G2-M phase. Moreover, the mechanism of action was determined by determining the topoisomerase inhibitory activity and the molecular modeling study. Compounds 3a,b,c,e showed broad spectrum anticancer activity. Lomefloxacin derivative 5f showed selective cytotoxic activity against melanoma SK-MEL-5 cell line. Compound 3e demonstrated comparable topoisomerase II inhibition to doxorubicin with IC50 of 0.98 µM.

Details

Title
Design, synthesis and in vitro anticancer activity of some new lomefloxacin derivatives
Author
Adly, Mina E. 1 ; Gedawy, Ehab M. 2 ; El-Malah, Afaf A. 1 ; Khalil, Omneya M. 1 

 Cairo University, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo, Egypt (GRID:grid.7776.1) (ISNI:0000 0004 0639 9286) 
 Cairo University, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo, Egypt (GRID:grid.7776.1) (ISNI:0000 0004 0639 9286); Badr University in Cairo, Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo, Egypt (GRID:grid.507995.7) (ISNI:0000 0004 6073 8904) 
Pages
6175
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2956991264
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.