Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids
El Wakil, M., Ghazala, R., El-Dershaby, H., Drozdowska, D., Wróbel-Tałałaj, A., Parzych, C., Ratkiewicz, A., Kolesińska, B., Abd El-Razik, H., Soliman, F. (2025). Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids. EKB Journal Management System, 3(2), 126-126. doi: 10.21608/ajst.2025.452260
Marwa El Wakil; Rasha A. Ghazala; Hadeel A. El-Dershaby; Danuta Drozdowska; Agnieszka Wróbel-Tałałaj; Cezary Parzych; Artur Ratkiewicz; Beata Kolesińska; Heba A. Abd El-Razik; Farid Soliman. "Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids". EKB Journal Management System, 3, 2, 2025, 126-126. doi: 10.21608/ajst.2025.452260
El Wakil, M., Ghazala, R., El-Dershaby, H., Drozdowska, D., Wróbel-Tałałaj, A., Parzych, C., Ratkiewicz, A., Kolesińska, B., Abd El-Razik, H., Soliman, F. (2025). 'Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids', EKB Journal Management System, 3(2), pp. 126-126. doi: 10.21608/ajst.2025.452260
El Wakil, M., Ghazala, R., El-Dershaby, H., Drozdowska, D., Wróbel-Tałałaj, A., Parzych, C., Ratkiewicz, A., Kolesińska, B., Abd El-Razik, H., Soliman, F. Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids. EKB Journal Management System, 2025; 3(2): 126-126. doi: 10.21608/ajst.2025.452260

Direct and Indirect DNA Targeting by Arylidene Hydrazinyl Thiazole Hybrids

Alexandria Journal of Science and Technology
Editor-in-Chief Lecture, Volume 3, Issue 2, September 2025, Pages 126-126
DOI: 10.21608/ajst.2025.452260
Authors
Marwa El Wakil* 1; Rasha A. Ghazala* 2; Hadeel A. El-Dershaby1; Danuta Drozdowska3; Agnieszka Wróbel-Tałałaj3; Cezary Parzych4; Artur Ratkiewicz4; Beata Kolesińska5; Heba A. Abd El-Razik1; Farid Soliman1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
2Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
3Department of Organic Chemistry, Medical University of Bialystok, Bialystok, Poland.
4Department of Physical Chemistry, University of Bialystok, Institute of Chemistry, Bialystok, Poland.
5Institute of Organic Chemistry, Lodz University of Technology, Lodz, Poland.
Abstract
In light of searching for new breast cancer therapies, DNA-targeted small molecules were rationally designed to simultaneously bind DNA and inhibit human dihydrofolate reductase (hDHFR). Fourteen new arylidene-hydrazinyl-1,3-thiazoles were synthesized and their dual DNA groove binding potential and in vitro hDHFR inhibition were performed. Two compounds proved their dual efficacy. Molecular docking and molecular dynamics simulations were performed for those active derivatives to explore their mode of binding and stability of interactions inside DHFR active site. Anti-breast cancer activity was assessed  on MCF-7 cells using MTX as reference. IC50 measurements revealed that both compounds were more potent and selective than MTX. Cytotoxicity was examined against normal skin fibroblasts to examine safety and selectivity. Moreover, mechanistic studies including apoptosis induction and wound healing were performed. Further in silico ADMET assessment was conducted to determine their eligibility as drug leads suitable for future optimization and development.
Keywords
Thiazoles; DNA; Cytotoxicity; Molecular modelling
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