MARC details
| 000 -LEADER |
|---|
| fixed length control field |
06298namaa22004451i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER |
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| control field |
EG-GICUC |
| 005 - أخر تعامل مع التسجيلة |
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| control field |
20251231095953.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
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| fixed length control field |
251230s2025 ua a|||frm||| 000 0 eng d |
| 040 ## - CATALOGING SOURCE |
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| 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 |
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| Acquisition Source |
Deposit |
| 082 04 - DEWEY DECIMAL CLASSIFICATION NUMBER |
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| Classification number |
615.19 |
| 092 ## - LOCALLY ASSIGNED DEWEY CALL NUMBER (OCLC) |
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| 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.2025.Kh.D |
| 100 0# - MAIN ENTRY--PERSONAL NAME |
|---|
| Authority record control number or standard number |
Khaled Alaa Mohamed Elsayad, |
| Preparation |
preparation. |
| 245 10 - TITLE STATEMENT |
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| Title |
Design, synthesis and quantitative determination of new zinc-binding carbonic anhydrase inhibitors / |
| Statement of responsibility, etc. |
by Khaled Alaa Mohamed Elsayad ; Supervision Prof. Dr. Fadi Mohsen Awadallah Erian, Prof. Dr. Sally Tarek Mahmoud, Prof. Dr. Ghada Fathy Elmasry. |
| 246 15 - VARYING FORM OF TITLE |
|---|
| Title proper/short title |
تصميم وتشييدوالتعيين الكمي لمثبطات جديدة من الكربونيك انهيدريز المرتبطة بالزنك |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE |
|---|
| Date of production, publication, distribution, manufacture, or copyright notice |
2025. |
| 300 ## - PHYSICAL DESCRIPTION |
|---|
| Extent |
112 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 : 106-112. |
| 520 #3 - SUMMARY, ETC. |
|---|
| Summary, etc. |
A comprehensive review of previously reported anticancer sulfonamides as carbonic <br/>anhydrase inhibitors was presented, emphasizing the effect of various moieties on the <br/>compound's affinity for the carbonic anhydrase active site. Additionally, dual-tail <br/>analogues of SLC-0111 were designed and synthesized as carbonic anhydrase inhibitors <br/>(CAIs) targeting tumor isoforms IX and XII (4a-h and 5a-h), accompanied by <br/>pharmacokinetic studies. <br/><br/> <br/><br/> The synthesized compounds were assessed for their inhibitory activity against four <br/>carbonic anhydrase isoforms (hCA I, II, IX, and XII), showing selective activity, <br/>especially against hCA IX and XII. Notably, compounds 4b, 5a, and 5b exhibited strong <br/>inhibition of hCA IX with Ki values of 20.4, 12.9, and 18.2 nM, respectively, compared <br/>to acetazolamide (AAZ) with a Ki of 25 nM. Additionally, compounds 5a, 5b, 5c, and <br/>5d demonstrated selective inhibition of hCA XII, with Ki values of 26.6, 8.7, 17.2, and <br/>10.9 nM, respectively, in comparison to AAZ (Ki = 5.7 nM). <br/><br/> <br/><br/>Furthermore, both series were evaluated for their anti-proliferative activity following <br/>the US-NCI protocol against a panel of over fifty cancer cell lines. <br/><br/> <br/><br/> Compound 5h met the activity criteria and was subsequently scheduled for further <br/>evaluation at five concentrations with 10-fold dilutions, revealing high toxicity against <br/>leukemia and lower toxicity against melanoma. Moreover, the MTT cytotoxicity assay <br/>was performed on compounds 5f, 5d, and acetazolamide using WI-38 normal cells. <br/><br/> <br/><br/>Additionally, an in vivo pharmacokinetic study was conducted using UPLC-MS/MS on <br/>the most potent derivative, 5d, demonstrating a pharmacokinetic profile comparable to <br/>the reference drug acetazolamide. Molecular docking studies were also performed on <br/>the most active compounds, 5d and 5h, to explore their interactions with the active site <br/>hot spots of the CA isoform IX and XII. |
| 520 #3 - SUMMARY, ETC. |
|---|
| Summary, etc. |
تركز هذه الدراسة على تصميم وتخليق وتقييم مشتقات بنزين سلفوناميد 4a-h,5a-h)) كمثبطات لإنزيم الكربونيك انهيدراز تم استخدام استراتيجية استبدال وامتداد الذيل بناءً على SLC-0111 لتحسين الفعالية والانتقائية مقارنةً بالأسيتازولاميد.<br/>• تثبيط إيزوفورمات إنزيم الكربونيك انهيدراز : تم تقييم المركبات المُصنعة ضد إيزوفورمات الأول، الثاني , التاسع و الثاني عشر أظهرت المركبات 4b , 5a و 5b نشاطًا مثبطًا متفوقًا، خاصة ضد الأيزو فورم التاسع ، حيث كانت قيم ثابت التثبيط للمركبات 20.4 و 12.9 و 18.9 نانومتر، على التوالي، متفوقة على الأسيتازولاميد حيث كانت قيمته 25 نانومتر.<br/>• تقييم النشاط المضاد للسرطان: تم اختبار مشتقات بنزين سلفوناميد ضد النشاط المضاد للسرطان. أظهر المركب 5d حساسية ممتازة ضد أنواع متعددة من السرطان، بما في ذلك اللوكيميا وسرطان الرئة، مع نسبة متوسط تثبيط النمو تبلغ 79.74 %.<br/>• المركب 5h استوفي معايير النشاط وتم تحديده للتقييم الإضافي عند خمسة تركيزات مع تخفيف بمقدار عشر اضعاف , حيث ظهر سمية عالية ضد اللوكيميا و سمية أقل ضد الميلانوما.<br/>• المركبات 5d , 5fأظهرت سمية خلوية أقل ضد خلايا WI-38 مقارنةً بالأسيتازولاميد، مما يشير إلى احتمال وجود ملف أمان أفضل للخلايا البشرية الطبيعية مقارنة بالأسيتازولاميد.<br/>• تم إجراء دراسة الإرساء الجزيئي للمركبات الأكثر نشاطًا 5d و 5h و ذلك لاستكشاف تفاعلاتهما مع الإنزيم انهيدراز الكربوني التاسع و الثاني عشر. |
| 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 الصيدلية |
| 653 #1 - INDEX TERM--UNCONTROLLED |
|---|
| Uncontrolled term |
Anticancer sulfonamides |
| -- |
Carbonic anhydrase inhibitors (CAIs) |
| -- |
Pharmacokinetic studies |
| -- |
Tumor isoforms IX and XII |
| -- |
Molecular docking |
| -- |
السولفوناميدات المضادة للسرطان |
| -- |
مثبطات إنزيم انهيدراز الكربوني |
| 700 0# - ADDED ENTRY--PERSONAL NAME |
|---|
| Personal name |
Fadi Mohsen Awadallah Erian |
| Relator term |
thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME |
|---|
| Personal name |
Sally Tarek Mahmoud |
| Relator term |
thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME |
|---|
| Personal name |
Ghada Fathy Elmasry |
| Relator term |
thesis advisor. |
| 900 ## - Thesis Information |
|---|
| Grant date |
01-01-2025 |
| Supervisory body |
Fadi Mohsen Awadallah Erian |
| -- |
Sally Tarek Mahmoud |
| -- |
Ghada Fathy Elmasry |
| Universities |
Cairo University |
| Faculties |
Faculty of Pharmacy |
| Department |
Department of Pharmaceutical Chemistry |
| 905 ## - Cataloger and Reviser Names |
|---|
| Cataloger Name |
Shimaa |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) |
|---|
| Source of classification or shelving scheme |
Dewey Decimal Classification |
| Koha item type |
Thesis |
| Edition |
21 |
| Suppress in OPAC |
No |