دورية أكاديمية
أعرض في EDS

Synthesis and in vitro investigation of novel cytotoxic pyrimidine and pyrazolopyrimidne derivatives showing apoptotic effect.

التفاصيل البيبلوغرافية
العنوان: Synthesis and in vitro investigation of novel cytotoxic pyrimidine and pyrazolopyrimidne derivatives showing apoptotic effect.
المؤلفون: Ragab FA; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo 11562, Egypt., Nissan YM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo 11562, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt., Seif EM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt. Electronic address: ph.emad.seif@gmail.com., Maher A; Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt., Arafa RK; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, 12578 Cairo, Egypt.
المصدر: Bioorganic chemistry [Bioorg Chem] 2020 Mar; Vol. 96, pp. 103621. Date of Electronic Publication: 2020 Jan 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: New York, London, Academic Press.
مواضيع طبية MeSH: Antineoplastic Agents/*chemistry , Antineoplastic Agents/*pharmacology , Pyrazoles/*chemistry , Pyrazoles/*pharmacology , Pyrimidines/*chemistry , Pyrimidines/*pharmacology, Antineoplastic Agents/chemical synthesis ; Apoptosis/drug effects ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; Models, Molecular ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Pyrazoles/chemical synthesis ; Pyrimidines/chemical synthesis
مستخلص: A series of novel derivatives of hydrazinylpyrimidines, pyrazolylpyrimidines and 3-amino[3,4-d]pyrazolopyrimidines have been synthesized and tested for their in vitro cytotoxic activity against 60 tumor cell lines by NCI. The in vitro cytotoxic IC 50 values for the most active compounds were determined against the colon-KM12 cell line (5d, 7c and 7d), breast-MCF-7 (6a) and melanoma-MDA-MB-435 (6h) using 5-fluorouracil (5-FU) as a positive control. Derivatives 5d and 7c were found to be the most potent derivatives against KM12 cell line (IC 50  = 1.73 and 1.21 µM, respectively) with a high selectivity index (SI) (18.82 and 35.49, respectively) compared to 5-FU (IC 50  = 12.26 µM, SI = 1.93). Compounds 5d and 7c were further investigated for their apoptotic behavior in KM12 cell line. The investigations showed the up-regulation of caspase 3/9 and the pro-apoptotic factor Bax. On the other hand, the expression of the anti-apoptotic factor Bcl-2, was down-regulated, as well as its inhibition at a nanomolar concentration. Furthermore, the apoptotic effect for derivatives 5d and 7c in KM12 cells was detected using annexin V-FITC staining method.
Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Apoptosis; Cytotoxicity; Pyrazolopyrimidine hybrids; Pyrimidine based hybrids
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Pyrazoles)
0 (Pyrimidines)
تواريخ الأحداث: Date Created: 20200210 Date Completed: 20210224 Latest Revision: 20210224
رمز التحديث: 20240628
DOI: 10.1016/j.bioorg.2020.103621
PMID: 32036162
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2120
DOI:10.1016/j.bioorg.2020.103621