Design, synthesis and biological evaluation of some nitrogenous based heterocyclic derivatives with anticipated anti-tumor activity / (Record no. 169228)
[ view plain ]
| 000 -LEADER | |
|---|---|
| fixed length control field | 08299namaa22004331i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20250223033337.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 241203s2023 |||a|||fr|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 | M.Sc |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.05.M.Sc.2023.Mo.D |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Moataz Magdy Farag Ahmed, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Design, synthesis and biological evaluation of some nitrogenous based heterocyclic derivatives with anticipated anti-tumor activity / |
| Statement of responsibility, etc. | by Moataz Magdy Farag Ahmed ; Supervised by Prof. Dr. Amal Abdel Haleem Eissa, Dr. Ahmed M. El Kerdawy, Dr. Walaa Ramadan Mahmoud. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | تصميم وتشييد والتقييم الحيوى لبعض المشتقات النيتروجينية الحلقية غير المتجانسة المتوقع لها فاعلية ضد الاورام السرطانية / |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2023. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 108 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, 2023. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 94-108. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Cancer is one of the most studied public health problems in the modern world, yet it is still one of the leading causes of death among developed countries. With multifactorial etiology counting both endogenous and exogenous factors as drivers for mutagenesis and carcinogenesis, tumoral cells often harbor hundreds of genomic alterations that lead to uncontrolled proliferation, differentiation, and expansion.<br/>EGFR and VEGFR are subtypes of receptor tyrosine kinases; EGFR dysregulation by overexpression, overactivation or mutation is associated with tumorigenesis, through the activation of several signal transduction and cellular processes and is correlated with poor prognosis in cancer patients. VEGFR kinases are another type of receptor tyrosine kinase involved in angiogenesis; it is mainly of three types VEGFR‐1, VEGFR-2, and VEGFR‐3. VEGFR inhibitors are widely used to treat various cancer types like pancreatic cancer, thyroid cancer, ovarian cancer, breast cancer, and NSCLC. <br/>Thus, the present investigation deals with design and synthesis of five new series of twenty-one quinazoline derivatives (Va-f, VIIIa,b, XIIa-e, XVIIa-e and XVIIIa-c) as kinase inhibitors against epidermal growth factor receptor (EGFR) and/or vascular epithelial growth factor receptor-2 (VEGFR-2) hoping to obtain new candidates with promising targeted anticancer activity and lower side effects.<br/>All the newly synthesized compounds were evaluated for their in vitro cytotoxicity against two human cancer cell lines namely: A549 (Lung) and Hep-G2 (Liver) using MTT method against sorafenib, the five compounds exhibiting potent dual inhibitory activity against both tested cell lines (XIId, XVIIc, XVIIe, XVIIIb and XVIIIc) were investigated for their safety against normal fibroblast cells WI-38 and then they were evaluated for their EGFR and VEGFR-2 inhibitory activity using Erlotinib and Sorafenib as reference standards, respectively.<br/> Favorably, the quinazoline derivative XVIIc showed a potent in vitro cytotoxic activity against A549 and Hep-G2 cell lines with an IC50 values of 6.83 and 4.71 µM, respectively. (Sorafenib IC50 = 14.96, 8.22 µM, respectively.)<br/> Additionally, XVIIc displayed comparable EGFR inhibition with an IC50 value of 6.32 nM compared to Erlotinib (IC50 = 2.09 nM) and superior VEGFR-2 inhibition with an IC50 value of 70.19 nM compared to Sorafenib (IC50 = 70.37 nM) and was subjected to cell cycle analysis and apoptotic assay at its IC50 leading to cell growth arrest at G1 phase in Hep-G2 cells after 24 h which was confirmed by an increase in the percentage of DNA content (57.32 %) after addition of the compound compared to the control cells (42.91 %) along with the decrease in the percentage of both S and G2/M phases. Furthermore, the percentage of the total apoptotic cells in Hep-G2 cell line has 22-fold increase after the treatment with compound XVIIc (44.61 %) relative to the control cells (2.14 %) which represents a prominent marker of apoptosis.<br/>To further investigate the activity of the most potent compounds, a molecular docking study was conducted to analyze their interaction with the active sites of EGFR (PDB: 1XKK) and VEGFR-2 (PDB: 3WZD). Furthermore, SwissADME was used to predict the physicochemical, ADME, and pharmacokinetic properties of these compounds.<br/> |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | السرطان هو أحد أكثر المشاكل الصحية التي تم دراستها في العالم الحديث، ومع ذلك فإنه لا يزال واحدًا من أسباب الوفاة الرئيسية ويعود ذلك إلى وجود عدة عوامل داخلية وخارجية تساهم في تحفيز عملية التحول الجيني وتشكيل السرطان، والتي تشمل العوامل الوراثية والبيئية. وعادة ما تحتوي خلايا الأورام على مئات التغييرات الجينية التي تؤدي إلى التكاثر غير المسيطر عليه والتمايز والانتشار .تعد مستقبلات EGFR و VEGFR نوعين من مستقبلات الكيناز الصمامية. وترتبط اضطرابات EGFR بالتحول الخبيث، وذلك عن طريق التعبير المفرط أو التحفيز المفرط أو التحول. وتسبب هذه الاضطرابات في تنشيط عدة عمليات نقل الإشارات والخلايا الداخلية، وترتبط بنتائج سيئة لدى مرضى السرطان. ومستقبلات VEGFR الكينازية هي نوع آخر من مستقبلات الكيناز الصمامية المشاركة في الأنجيوجينيز، وتتألف بشكل رئيسي من ثلاثة أنواع: VEGFR-1 و VEGFR-2 و VEGFR-3. وتستخدم مثبطات VEGFR على نطاق واسع لعلاج مختلف أنواع السرطانات مثل سرطان البنكرياس وسرطان الغدة الدرقية وسرطان المبيض وسرطان الثدي وسرطان الرئة غير الصغيرة.<br/>وبناءً على ذلك ، تتناول هذه الدراسة تشييد بعض من مشتقات الكينازولين Va-f و VIIIa,b، XIIa-e، XVIIa-e و XVIIIa-c كمثبطات للكيناز ضد مستقبلات EGFR و / أو VEGFR-2، بهدف الحصول على مركبات جديدة ذات فعالية مستهدفة مضادة للسرطان وآثار جانبية أقل.<br/>تم تقييم جميع المركبات الجديدة المصنعة لتحديد فاعليتها ضد خلايا سرطانية بشرية، وهما: A549 (الرئة) و Hep-G2 (الكبد) باستخدام طريقة MTT. وتم دراسة المركبات الخمسة التي أظهرت نشاطًا مثبطًا ثنائيًا قويًا ضد الخلايا المختبرة المذكورة (XIId و XVIIc و XVIIe وXVIIIb و XVIIIc) لتحديد سلامتها ضد الخلايا الطبيعية WI-38، ثم تم تقييمها لنشاطها المثبط لمستقبلات EGFR و VEGFR-2.<br/>علاوة على ذلك ، أجريت نمذجة جزيئية لدراسة الإرساء الجزيئي لبعض المركبات الجديدة المختارة مع الموقع النشط للإنزيم مع توقع خصائصهم الفيزيائية والكيميائية والحركية الدوائية.<br/> |
| 530 ## - ADDITIONAL PHYSICAL FORM AVAILABLE NOTE | |
| Issues CD | Issued 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 | Quinazoline |
| -- | Anticancer activity |
| -- | Breast cancer |
| -- | Lapatinib |
| -- | Sorafenib |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Amal Abdel Haleem Eissa |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ahmed M. El Kerdawy |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Walaa Ramadan Mahmoud |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2023 |
| Supervisory body | Amal Abdel Haleem Eissa |
| -- | Ahmed M. El Kerdawy |
| -- | Walaa Ramadan Mahmoud |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmaceutical Chemistry |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Eman Ghareeb |
| 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 | 03.12.2024 | 89107 | Cai01.08.05.M.Sc.2023.Mo.D | 01010110089107000 | 03.12.2024 | 03.12.2024 | Thesis |