Design, synthesis and biological evaluation of new substituted pyrazole derivatives targeted as anticancer agents / (Record no. 176137)
[ view plain ]
| 000 -LEADER | |
|---|---|
| fixed length control field | 05577namaa22004451i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | EG-GICUC |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20251217102140.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 251123s2024 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 | M.Sc |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.05.M.Sc.2024.Sa.D |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Samar Mahmoud El sayed Mogheith, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Design, synthesis and biological evaluation of new substituted pyrazole derivatives targeted as anticancer agents / |
| Statement of responsibility, etc. | by Samar Mahmoud El Sayed Mogheith ; Supervised Dr. Heba Abdelrasheed Abdelkhalek, Dr. Samy Mohamady Mohamady Ahmed, Dr. Manal Abdel Fattah Ezzat. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | تصميم وتشييد وتقييم بيولوجي لمشتقات بيرازول جديدة مستهدفة كعوامل مضادة للسرطان |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2025. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 143 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 (M.Sc)-Cairo University, 2025. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 115-143. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | A series of novel 1H-pyrazolo[3,4-b]pyridine-5carbonitrile derivatives were designed, synthesized, and biologically evaluated as Kinase inhibitors and anticancer agents.<br/>The efficacy of the target compounds as anticancer agents was assisted through in vitro screening against NCI 60 cell lines. To figure out the kinase inhibitory activity, the most potent compounds IIIfand IIIo were screened against 20 kinases using tucatinib as a reference compound. HER2 was specifically targeted by IIIf and IIIo, which inhibited it with an inhibition percentages of -88% and -79%, respectively. Both compounds IIIf and IIIo were tested at 10 concentrations (ranging from 0.05 µM to 250 µM) against HER2 protein kinase to determine their IC50 values. Furthermore, the antiproliferative effects of the newly target compounds were screened using MTT assay against three HER2-expressing breast cancer (BC) cell lines (BT474, BT549, and ZR753) using lapatinib as a positive control. All target compounds revealed statistically significant potent antiproliferative activities with IC50 ranging from lower to sub micromolar levels. <br/>Moreover, an apoptosis assay was conducted for the most potent compounds namely IIIf, IIIl and IIIo againstBT474 cell line at 0.5, 1.0, 5.0, and 10 µM concentrations.<br/>Finally, the most potent compound IIIf, was in vivo tested for its anticancer activity.<br/>Moreover, a molecular modeling study was performed to understand the interaction and stability of the newly synthesized compounds with the active site of HER2. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | تم تصميم سلسلة من مشتقات 1H-pyrazolo[3,4-b]pyridine-5carbonitrile الجديدة وتصنيعها وتقييمها بيولوجيًا كمثبطات kinase وعوامل مضادة للسرطان. <br/>تم فحص فعالية المركبات المستهدفة كعوامل مضادة للسرطان من خلال الفحص المختبري ضد خلايا (NCI). لمعرفة النشاط المثبط للkinase ، تم فحص المركبات الأكثر فعالية IIIf وIIIo مقابل 20 kinase باستخدام التوكاتينيب كمركب مرجعي. تم ملاحظة انه تم استهداف HER2 على وجه التحديد بواسطة IIIf وIIIo، مما أدى إلى تثبيطه بنسب تثبيط تبلغ -88% و-79% على التوالي. <br/>تم اختبار كلا المركبين IIIf وIIIo عند 10 تركيزات (تتراوح من 0.05 µM إلى 250 µM) ضد بروتين kinaseHER2 لتحديد قيم IC50 الخاصة بهما. علاوة على ذلك، تم فحص التأثيرات المضادة للتكاثر للمركبات باستخدام اختبار MTT ضد ثلاثة خطوط خلايا لسرطان الثدي تحتوي على Her2 (BT474، BT549، وZR753) باستخدام اللاباتينيب كعنصر تحكم إيجابي. <br/>كشفت جميع المركبات المستهدفة عن أنشطة مضادة للتكاثر قوية ذات دلالة إحصائية مع IC50 تتراوح من مستويات أقل إلى دون الميكرومولار. <br/>كما تم دراسة التأثير السمي للمشتقات التي أظهرت فاعلية تجاه خلايا السرطان على خلايا BT474 الموجودة في سرطان الثدي. بالاضافة الى قياس تأثير افضل مركب على فئران مصابة بالسرطان. علاوة على ذلك، أجريت نمذجة جزيئية لدراسة الإرساء الجزيئي للمركبات الجديدة مع الموقع النشط للإنزيم. |
| 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 الصيدليه |
| 653 #1 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Pyrazolopyridinederivatives |
| -- | kinase inhibitors |
| -- | Her2 inhibitors |
| -- | anticancer |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Heba Abdelrasheed Abdelkhalek |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Samy Mohamady Mohamady Ahmed |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Manal Abdel Fattah Ezzat |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2024 |
| Supervisory body | Heba Abdelrasheed Abdelkhalek |
| -- | Samy Mohamady Mohamady Ahmed |
| -- | Manal Abdel Fattah Ezzat |
| 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 | 23.11.2025 | 92561 | Cai01.08.05.M.Sc.2024.Sa.D | 01010110092561000 | 23.11.2025 | 23.11.2025 | Thesis |