Pyridazinone-based derivatives as anticancer agents endowed with anti-microbial activity: molecular design, synthesis, and biological investigation.
| Autor: | El-Nagar MKS; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City Sadat City Menoufia 32897 Egypt., Shahin MI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University Abbassia Cairo 11566 Egypt Dalal@pharma.asu.edu.eg Khaled.abouzid@pharma.asu.edu.eg., El-Behairy MF; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City Sadat City Menoufia 32897 Egypt., Taher ES; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University Assiut 71524 Egypt.; Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University Zarqa 13110 Jordan., El-Badawy MF; Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City Sadat City Menoufia 32897 Egypt., Sharaky M; Department of Cancer Biology, Pharmacology Unit, National Cancer Institute (NCI), Cairo University Cairo Egypt., Abou El Ella DA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University Abbassia Cairo 11566 Egypt Dalal@pharma.asu.edu.eg Khaled.abouzid@pharma.asu.edu.eg., Abouzid KAM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University Abbassia Cairo 11566 Egypt Dalal@pharma.asu.edu.eg Khaled.abouzid@pharma.asu.edu.eg., Adel M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University Abbassia Cairo 11566 Egypt Dalal@pharma.asu.edu.eg Khaled.abouzid@pharma.asu.edu.eg. |
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| Jazyk: | angličtina |
| Zdroj: | RSC medicinal chemistry [RSC Med Chem] 2024 Aug 16. Date of Electronic Publication: 2024 Aug 16. |
| DOI: | 10.1039/d4md00481g |
| Abstrakt: | Cancer patients undergoing chemotherapy are highly susceptible to infections owing to their compromised immune system, which also promotes cancer progression through inflammation. Thus, this study aimed to develop novel chemotherapeutic agents with both anticancer and antimicrobial properties. A series of diarylurea derivatives based on pyridazinone scaffolds were designed, synthesized, and characterized as surrogates for sorafenib. The synthesized compounds were tested for their antimicrobial activity and screened against 60 cancer cell lines at the National Cancer Institute (NCI). Compound 10h exhibited potent antibacterial activity against Staphylococcus aureus (MIC = 16 μg mL -1 ), whereas compound 8g showed significant antifungal activity against Candida albicans (MIC = 16 μg mL -1 ). Additionally, ten compounds were further evaluated for VEGFR-2 inhibition, with compound 17a showing the best inhibitory activity. Compounds 8f, 10l, and 17a demonstrated significant anticancer activity against melanoma, NSCLC, prostate cancer, and colon cancer, with growth inhibition percentages (GI%) ranging from 62.21% to 100.14%. Compounds 10l and 17a were selected for five-dose screening, displaying GI Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. (This journal is © The Royal Society of Chemistry.) |
| Databáze: | MEDLINE |
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