دورية أكاديمية
أعرض في EDS

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

التفاصيل البيبلوغرافية
العنوان: Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.
المؤلفون: El Sayed D; Chemistry Department, Faculty of Science, Suez Canal University P.O. 41522 Ismailia Egypt mohamed_nafie@science.suez.edu.eg samir_elrayes@science.suez.edu.eg., El Rayes SM; Chemistry Department, Faculty of Science, Suez Canal University P.O. 41522 Ismailia Egypt mohamed_nafie@science.suez.edu.eg samir_elrayes@science.suez.edu.eg., Soliman HA; Chemistry Department, Faculty of Science, Suez Canal University P.O. 41522 Ismailia Egypt mohamed_nafie@science.suez.edu.eg samir_elrayes@science.suez.edu.eg., AlBalaa IE; Science Department, Faculty of Basic Educations, PAAET Kuwait Safat 22081 Kuwait., Alturki MS; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University P.O. Box 1982 Dammam 31441 Eastern Province Kingdom of Saudi Arabia., Al Khzem AH; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University P.O. Box 1982 Dammam 31441 Eastern Province Kingdom of Saudi Arabia., Alsharif MA; King Fahad Armed Forces Hospital Al Kurnaysh Rd, Al Andalus Jeddah 23311 Kingdom of Saudi Arabia., Nafie MS; Chemistry Department, Faculty of Science, Suez Canal University P.O. 41522 Ismailia Egypt mohamed_nafie@science.suez.edu.eg samir_elrayes@science.suez.edu.eg.; Department of Chemistry, College of Sciences, University of Sharjah P.O. 27272 Sharjah United Arab Emirates mohamed.elsayed@sharjah.ac.ae.
المصدر: RSC advances [RSC Adv] 2024 Apr 24; Vol. 14 (19), pp. 13027-13043. Date of Electronic Publication: 2024 Apr 24 (Print Publication: 2024).
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: The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1 H )-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective N -alkylation via addition reaction of 4-benzylphthalazin-1(2 H )-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1 H )-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1 H )-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c. The hydrazide 9a was subjected to the azide coupling procedure, which resulted in the formation of various dipeptides. Subsequently, it was condensed with various aldehydes to yield hydrazone derivatives 13a-d. Interestingly, compounds 9c, 12b, and 13c exhibited potent cytotoxicity with IC 50 values of 1.58, 0.32 and 0.64 μM compared to sorafenib (IC 50 = 2.93 μM). Compound 12b exhibited potent VEGFR2 inhibition by 95.2% with an IC 50 value of 17.8 μM compared to sorafenib (94.7% and IC 50 of 32.1 μM). For apoptosis activity, 12b-treatment induced apoptosis in HCT-116 cells by 21.7-fold, arresting the cell proliferation at S-phase. Finally, it formed a good binding affinity towards VEGFR2 protein with a binding energy of -10.66 kcal mol -1 , and it formed binding interactions with the key interactive amino acids.
Competing Interests: The authors declare no conflict of interest.
(This journal is © The Royal Society of Chemistry.)
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تواريخ الأحداث: Date Created: 20240425 Latest Revision: 20240426
رمز التحديث: 20240426
مُعرف محوري في PubMed: PMC11040327
DOI: 10.1039/d4ra02103g
PMID: 38660526
قاعدة البيانات: MEDLINE
الوصف
تدمد:2046-2069
DOI:10.1039/d4ra02103g