Synthesis, Synthesis, anticancer activity and molecular docking studies of novel pyrimidine derivatives as potential multikinase inhibitors / (Record no. 170282)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 05998namaa22004451i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20250223033414.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 250119s2024 |||a|||f m||| 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.2024.Mu.S |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Mustafa Abdualsalam Saed Al- Qadhi, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Synthesis, Synthesis, anticancer activity and molecular docking studies of novel pyrimidine derivatives as potential multikinase inhibitors / |
| Statement of responsibility, etc. | by Mustafa Abdualsalam Saed Al- Qadhi ; Supervision of Prof. Dr. Fatma Abd El-Fattah Ragab, Prof. Dr.Tawfeek Ahmad Ali Yahya, Dr. Samar Hashem Fahim, Dr. Heba Abdelrasheed Abdelkhalek. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | / تشيد واختبار النشاط المضاد للأورام السرطانية ودراسة الارساء الجزيئي لمشتقات البيريميدين الجديدة كمثبطات محتملة لإنزيمات الكاينيز المتعددة |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2024. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 133 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, 2024. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 119-133. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Pyrazolo[1,5-a]pyrimidines are recognized for their extensive range of<br/>biological activities, particularly their noteworthy anticancer properties. The cytotoxic activity of this framework is attributed to its ability to function as a bioisostere of adenine, thereby preserving the principal ATP interaction within the kinase domain. Furthermore, pyrazolo[1,5-a]pyrimidines have demonstrated inhibitory activity against various protein kinases including both tyrosine kinases (TKs) and a diverse array of serine threonine kinases(STKs).<br/>In the present investigation four new series 7a-e, 8a-e, 9a-e, and 10a-e of 7- aryl-3-substituted pyrazolo[1,5-a]pyrimidines were synthesized and tested for their RTK and STK inhibitory activity. Compound 7d demonstrated potent enzymatic inhibitory activity against TrkA and ALK2 with IC50 0.087and 0.105 μM, respectively, and potent Anti-proliferative activity against KM12 and EKVX cell lines with IC50 0.82 and 4.13 μM, respectively. Compound 10e showed good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2 in sub-micromolar values. Additionally 10e revealed anti-proliferative activity against MCF7, HCT116 and EKVX with IC50 3.36, 1.40 and 3.49 μM, respectively; with good safety profile. Moreover, 10e showed cell cycle arrest at the G1/S and G1 phases in MCF7 and HCT116 cells with good apoptotic effect. Molecular docking studies were fulfilled for compound 10e and illustrated good interaction with the hot spots of the active site of the tested enzymes. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | تعرف بيرزولوبيريميدين بنطاقها الواسع من الأنشطة البيولوجية، ولا سيما خصائصها المضادة للسرطان الجديرة بالملاحظة. يُعزى النشاط السام ضد الخلايا لهذا الإطار إلى قدرته على العمل كإيزوستير حيوي للأدينين، وبالتالي الحفاظ على تفاعل ادينوسين ثلاثي الفوسفات الرئيسي داخل مجال الكيناز. علاوة على ذلك، أظهر البايرازولوبيريميدين نشاطًا مثبطًا ضد كينازات البروتين المختلفة بما في ذلك كينيز التيروزين (TKs) ومجموعة متنوعة من كينيزات ثريونين السيرين (STKs)<br/>في البحث الحالي، تم تصنيع أربع سلاسل جديدة a-e)7( و a-e)8( و (9a-e) و(10a-e) من 7-أريل-3 بيرازولوبيريميدين واختبارها من حيث تثبيط نشاط التيروزين كينيز RTK و ثرونين كينيز STK. أظهر المركب 7d نشاطًا مثبطًا إنزيميًا قويًا ضد TrkA وALK2 مع IC50 0.087 و0.105 ميكرومول ، على التوالي، ونشاطًا قويًا مضادًا للتكاثر ضد الخلايا السرطانية KM12 وEKVX مع IC50 0.82 ميكرومول ، على التوالي وأظهر المركب 10e نشاطًا مثبطًا جيدًا للإنزيم ضد TrkA وALK2 وc-KIT وEGFR وPIM1 وCK2α وCHK1 وCDK2 في القيم دون الميكرومولار. بالإضافة إلى ذلك، كشف 10e عن نشاط مضاد للتكاثر ضد الخلايا السرطانية MCF7 وHCT116 وEKVX مع IC50 3.36 و1.40 و3.49 ميكرو مول على التوالي؛ مع ملف تعريف أمان جيد<br/>علاوة على ذلك، أظهر 10e توقف دورة الخلية في الطور G1/S والمرحلة G1 في خلايا MCF7 وHCT116 مع تأثير موت الخلايا المبرمج الجيد. تم إجراء دراسات الارساء الجزيئي للمركب 10e وأوضحت التفاعل الجيد مع النقاط الساخنة للموقع النشط للإنزيمات المختبرة |
| 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 #7 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | Pharmaceutical Chemistry |
| Source of heading or term | qrmak |
| 653 #0 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Pyrazolopyrimidine |
| -- | anticancer |
| -- | kinase inhibitors TRKs |
| -- | RTKs |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Fatma Abd El-Fattah Ragab |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Tawfeek Ahmad Ali Yahya |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Samar Hashem Fahim |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Heba Abdelrasheed Abdelkhalek |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2024 |
| Supervisory body | Fatma Abd El-Fattah Ragab |
| -- | Tawfeek Ahmad Ali Yahya |
| -- | Samar Hashem Fahim |
| -- | Heba Abdelrasheed Abdelkhalek |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmaceutical Chemistry |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Shimaa |
| Reviser Names | Huda |
| 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 | 19.01.2025 | 90263 | Cai01.08.05.Ph.D.2024.Mu.S | 01010110090263000 | 19.01.2025 | 19.01.2025 | Thesis |