دورية أكاديمية
أعرض في EDS

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity.

التفاصيل البيبلوغرافية
العنوان: Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity.
المؤلفون: Ahmed NM; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Ein-Helwan, Helwan, Cairo 11795, Egypt., Youns MM; Biochemistry Department, Faculty of Pharmacy, Helwan University, Ein-Helwan, Helwan, Cairo 11795, Egypt.; Oman College of Health Sciences, Muscat 123, Oman., Soltan MK; Oman College of Health Sciences, Muscat 123, Oman.; Medicinal Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt., Said AM; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Ein-Helwan, Helwan, Cairo 11795, Egypt.; Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2021 Mar 25; Vol. 26 (7). Date of Electronic Publication: 2021 Mar 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Antineoplastic Agents*/chemical synthesis , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/pharmacology , Models, Molecular* , Neoplasm Proteins*/antagonists & inhibitors , Neoplasm Proteins*/metabolism , Pyrimidines*/chemical synthesis , Pyrimidines*/chemistry , Pyrimidines*/pharmacology, Neoplasms/*drug therapy, Animals ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; HCT116 Cells ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Mice ; Neoplasms/metabolism ; Neoplasms/pathology ; Xenograft Model Antitumor Assays
مستخلص: Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1 - 4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC 50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53-79%) activity. Compound 4g was found to be the most active compound against EGFR (IC 50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.
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فهرسة مساهمة: Keywords: EGFR; cancer; drug design; indole; molecular modeling; pyrimidine
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Neoplasm Proteins)
0 (Pyrimidines)
EC 2.7.10.1 (EGFR protein, human)
EC 2.7.10.1 (ErbB Receptors)
تواريخ الأحداث: Date Created: 20210403 Date Completed: 20210512 Latest Revision: 20210512
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8037142
DOI: 10.3390/molecules26071838
PMID: 33805918
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules26071838