New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Hamada H. H. Mohammed; Amer Ali Abd El-Hafeez; Kareem Ebeid; Aml I. Mekkawy; Mohammed A. S. Abourehab; Emad I. Wafa; Suhaila O. Alhaj-Suliman; Aliasger K. Salem; Pradipta Ghosh; Gamal El-Din A. Abuo-Rahma; Alaa M. Hayallah; Samar H. Abbas

doi:10.1080/14756366.2022.2072308

Back

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Journal article

Open access

Peer reviewed

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

Hamada H. H. Mohammed, Amer Ali Abd El-Hafeez, Kareem Ebeid, Aml I. Mekkawy, Mohammed A. S. Abourehab, Emad I. Wafa, Suhaila O. Alhaj-Suliman, Aliasger K. Salem, Pradipta Ghosh, Gamal El-Din A. Abuo-Rahma, …

Journal of enzyme inhibition and medicinal chemistry, Vol.37(1), pp.1346-1363

12/31/2022

DOI: 10.1080/14756366.2022.2072308

PMCID: PMC9116245

PMID: 35548854

Files and links (1)

url

https://doi.org/10.1080/14756366.2022.2072308View

Published (Version of record) Open Access

Abstract

A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC 50 s ranged from 2.53-8.67 µM, 8.67-62.47 µM, and 4.19-24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC 50 values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC 50 values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC 50 = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.

chalcone

ciprofloxacin

Click synthesis

cytotoxicity

DNA damage

HCT116 cells

topoisomerase I and II inhibitors

tubulin polymerisation inhibition

Details

Title: Subtitle: New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization
Creators: Hamada H. H. Mohammed - Sohag University
Amer Ali Abd El-Hafeez - Cairo University
Kareem Ebeid - Minia University
Aml I. Mekkawy - Sohag University
Mohammed A. S. Abourehab - Department of Pharmaceutics, Faculty of Pharmacy, Umm Al Qura University
Emad I. Wafa - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa
Suhaila O. Alhaj-Suliman - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa
Aliasger K. Salem - University of Iowa
Pradipta Ghosh - Veterans Affairs Medical Center
Gamal El-Din A. Abuo-Rahma - Minia University
Alaa M. Hayallah - Sphinx (Netherlands)
Samar H. Abbas - Minia University
Resource Type: Journal article
Publication Details: Journal of enzyme inhibition and medicinal chemistry, Vol.37(1), pp.1346-1363
DOI: 10.1080/14756366.2022.2072308
PMID: 35548854
PMCID: PMC9116245
NLM abbreviation: J Enzyme Inhib Med Chem
ISSN: 1475-6366
eISSN: 1475-6374
Publisher: Taylor & Francis
Language: English
Date published: 12/31/2022
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984258460302771

Metrics

75 Record Views

39 Times Cited - Web of Science