دورية أكاديمية
أعرض في EDS

Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives as novel anti-cancer, dual EGFR WT /COX-2 inhibitors with docking studies.

التفاصيل البيبلوغرافية
العنوان: Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives as novel anti-cancer, dual EGFR WT /COX-2 inhibitors with docking studies.
المؤلفون: Reda N; Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST) 6th of October City Egypt amira.helwa@must.edu.eg Nada.reda@must.edu.eg., Elshewy A; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University Kasr El-Aini Street Cairo 11562 Egypt khaled.mohamed@pharma.cu.edu.eg ahmed.elshewy@pharma.cu.edu.eg.; Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University New Galala 43713 Egypt., El-Askary HI; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University Kasr El-Aini Street Cairo 11562 Egypt hesham.elaskary@pharma.edu.eg., Mohamed KO; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University Kasr El-Aini Street Cairo 11562 Egypt khaled.mohamed@pharma.cu.edu.eg ahmed.elshewy@pharma.cu.edu.eg.; Pharmaceutical Chemistry Department, Faculty of Pharmacy. Sinai University (Arish Branch) El Arish Egypt., Helwa AA; Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST) 6th of October City Egypt amira.helwa@must.edu.eg Nada.reda@must.edu.eg.
المصدر: RSC advances [RSC Adv] 2023 Nov 02; Vol. 13 (46), pp. 32296-32320. Date of Electronic Publication: 2023 Nov 02 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101581657 Publication Model: eCollection Cited Medium: Internet ISSN: 2046-2069 (Electronic) Linking ISSN: 20462069 NLM ISO Abbreviation: RSC Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Cambridge [England] : Royal Society of Chemistry, [2011]-
مستخلص: A novel series of pyrimidine-5-carbonitrile derivatives was designed, synthesized, then evaluated for their cytotoxic activity as novel anti-cancer with dual EGFR WT /COX-2 inhibitors. Two compounds 4e and 4f disclosed the highest activity against all NCI60 panel cell lines. They were most potent against Colo 205 (IC 50 = 1.66, and 1.83 μM), Sequentially. The most potent two compounds disturbed cell cycle of Colo-205 cells by blocking the G1 phase, coupled with increased annexin-Vstained cells which indicated the increasing in percentage of apoptosis. In addition, 4e and 4f increase the concentration of caspase-3 by 10, and 8-fold compared to control, respectively. Moreover, the two candidate compounds were screened for cytotoxicity on normal epithelial colon cells; fortunately, they were found to be safe. Molecular docking study displayed that these compounds bound to the active site as EGFR WT /COX-2 inhibitors. Furthermore, 3D pharmacophore mapping disclosed many shared features between the most potent candidates 4e and 4f and the standard EGFR WT /COX-2 inhibitors; erlotinib, and celecoxib, respectively. Finally, the physicochemical parameter was calculated for the most potent novel anticancer candidates and the SwissAdme parameter showed that the newly synthesized compounds have good drug-likeness properties.
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 paper.
(This journal is © The Royal Society of Chemistry.)
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تواريخ الأحداث: Date Created: 20231106 Latest Revision: 20231107
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10620772
DOI: 10.1039/d3ra06088h
PMID: 37928843
قاعدة البيانات: MEDLINE
الوصف
تدمد:2046-2069
DOI:10.1039/d3ra06088h