Design, synthesis and biological evaluation of some novel furo[2,3-d]pyrimidine derivatives as protein kinase inhibitors / (Record no. 173675)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 05836namaa22004331i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20250922110430.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 250824s2025 ua a|||frm||| 000 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Original cataloguing agency | EG-GICUC |
| Language of cataloging | eng |
| Transcribing agency | EG-GICUC |
| Modifying agency | EG-GICUC |
| Description conventions | rda |
| 041 0# - LANGUAGE CODE | |
| Language code of text/sound track or separate title | eng |
| Language code of summary or abstract | eng |
| -- | ara |
| 049 ## - Acquisition Source | |
| Acquisition Source | Deposit |
| 082 04 - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 615.19 |
| 092 ## - LOCALLY ASSIGNED DEWEY CALL NUMBER (OCLC) | |
| Classification number | 615.19 |
| Edition number | 21 |
| 097 ## - Degree | |
| Degree | Ph.D |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.05.Ph.D.2025.Ma.D |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Manar Abd Elkarim kassem Ezz Eldin, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Design, synthesis and biological evaluation of some novel furo[2,3-d]pyrimidine derivatives as protein kinase inhibitors / |
| Statement of responsibility, etc. | by Manar Abd Elkarim kassem Ezz Eldin ; Supervised Prof. Dr. Safinaz El-Sayed Abbas Ibrahim, Dr. Akram Hifny Abd El-Haleem. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | تصميم وتشييد وتقييم النشاط بيولوجي لبعض مشتقات الفورو[2،3-د] بيريميدين الجديدة كمثبطات لبروتين كينيز |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2025. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 94 pages : |
| Other physical details | illustrations ; |
| Dimensions | 25 cm. + |
| Accompanying material | CD. |
| 336 ## - CONTENT TYPE | |
| Content type term | text |
| Source | rda content |
| 337 ## - MEDIA TYPE | |
| Media type term | Unmediated |
| Source | rdamedia |
| 338 ## - CARRIER TYPE | |
| Carrier type term | volume |
| Source | rdacarrier |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | Thesis (Ph.D)-Cairo University, 2025. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 83-94. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | The present study involves the design and synthesis of twenty five compounds IVa-d, VI, VIIa-d, <br/>VIIIa-c, IX, XIa,b, XIIa-f, XIIIa-c and XIV to be evaluated for their VEGFR-2 inhibitory activity . <br/>Compounds IVc, VIIb, and VIIc showing a significant enzyme inhibition (IC50 = 57.14, 42.45 and 52.5 <br/>nM), respectively, compared to sorafenib (IC50 = 41.07 nM) were further assessed for their cytotoxicity <br/>against human liver (HepG2), breast (MCF-7), lung (A549), colon (HT-29) and prostate (PC3) cancer cell <br/>lines in addition to the normal cell line WI-38. Compound VIIb displayed a nearly equipotent cytotoxicity <br/>against A549 and HT-29 (IC50 = 6.66 and 8.51 µM), respectively, compared to sorafenib (IC50 = 6.60 and <br/>8.78 µM). Compound VIIb was subjected to cell cycle analysis and apoptosis assay on HT-29, where it <br/>caused cell cycle arrest at G2/M phase and elevation of total apoptosis. Apoptotic induction was further <br/>confirmed by an increase in Bax and a decrease in Bcl2 than untreated cells. Also, Western blot analysis of <br/>VIIb at three different concentrations (0.1 IC50, 0.5 IC50 and IC50) revealed the inhibition and deactivation <br/>of VEGFR-2 in a dose dependent manner. Moreover, wound healing assay of VIIb showed a noticeable <br/>inhibition in wound closure. A molecular docking study was carried out on the most active compounds <br/>IVc, VIIb, and VIIc in the active site of the enzyme to get insight of their binding mode, in addition to <br/>molecular dynamics simulation of IVc and VIIb. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | تتضمن هذه الدراسة تصميم وتخليق خمسة وعشرين مركبًا، هي IVa-d، وVIIa-d، وVIIIa-c، وIX، وXIa,b، وXIIa-f، وXIIIa-c، وXIV، لتقييم نشاطها المثبط لمستقبل عامل نمو بطانة الأوعية الدموية من النوع 2 (VEGFR-2). وقد خضعت المركبات IVc، وVIIb، وVIIc، التي أظهرت تثبيطًا إنزيميًا ملحوظًا (IC50 = 57.14، و42.45، و52.5 نانومول) على التوالي، مقارنةً بالسورافينيب (IC50 = 41.07 نانومول)، لمزيد من التقييم لسميتها الخلوية ضد سلالات خلايا سرطان الكبد البشري (HepG2)، والثدي (MCF-7)، والرئة (A549)، والقولون (HT-29)، والبروستاتا (PC3)، بالإضافة إلى سلالة الخلايا الطبيعية WI-38. أظهر المركب VIIb سمية خلوية شبه متساوية الفعالية ضد A549 وHT-29 (IC50 = 6.66 و8.51 ميكرومولار)، على التوالي، مقارنةً بالسورافينيب (IC50 = 6.60 و8.78 ميكرومولار). خضع المركب VIIb لتحليل دورة الخلية واختبار موت الخلايا المبرمج على HT-29، حيث تسبب في توقف دورة الخلية في الطور G2/M وارتفاع معدل موت الخلايا المبرمج الكلي. وتم تأكيد تحريض موت الخلايا المبرمج بشكل أكبر من خلال زيادة Bax وانخفاض Bcl2 مقارنةً بالخلايا غير المعالجة. كما كشف تحليل لطخة ويسترن للمركب VIIb عند ثلاثة تركيزات مختلفة (0.1 IC50، 0.5 IC50 وIC50) عن تثبيط وتعطيل مستقبل عامل نمو بطانة الأوعية الدموية 2 (VEGFR-2) بطريقة تعتمد على الجرعة. علاوة على ذلك، أظهر اختبار التئام الجروح للمركب VIIb تثبيطًا ملحوظًا في التئام الجروح. تم إجراء دراسة الالتحام الجزيئي على المركبات الأكثر نشاطًا IVc وVIIb وVIIc في الموقع النشط للإنزيم للحصول على فكرة عن طريقة ارتباطها، بالإضافة إلى محاكاة الديناميكيات الجزيئية لـ IVc وVIIb. |
| 530 ## - ADDITIONAL PHYSICAL FORM AVAILABLE NOTE | |
| Issues CD | Issues also as CD. |
| 546 ## - LANGUAGE NOTE | |
| Text Language | Text in English and abstract in Arabic & English. |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | Pharmaceutical Chemistry |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | الكيمياء الصيدلانية |
| 653 #1 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Furan |
| -- | Furopyrimidine |
| -- | VEGFR-2 |
| -- | Cytotoxicity |
| -- | Sorafenib |
| -- | A549 |
| -- | HT-29 |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Safinaz El-Sayed Abbas Ibrahim |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Akram Hifny Abd El-Haleem |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2025 |
| Supervisory body | Safinaz El-Sayed Abbas Ibrahim |
| -- | Akram Hifny Abd El-Haleem |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmaceutical Chemistry |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Shimaa |
| Reviser Names | Eman Ghareb |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Dewey Decimal Classification |
| Koha item type | Thesis |
| Edition | 21 |
| Suppress in OPAC | No |
| Source of classification or shelving scheme | Home library | Current library | Date acquired | Inventory number | Full call number | Barcode | Date last seen | Effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|
| Dewey Decimal Classification | المكتبة المركزبة الجديدة - جامعة القاهرة | قاعة الرسائل الجامعية - الدور الاول | 24.08.2025 | 91916 | Cai01.08.05.Ph.D.2025.Ma.D | 01010110091916000 | 24.08.2025 | 24.08.2025 | Thesis |