Thiazolidinone derivatives : (Record no. 171370)
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| 000 -LEADER | |
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| fixed length control field | 09155namaa22004331i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20250427104446.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 250408s2024 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.2024.Mo.T |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Mona Ahmed Gamal Eldien Teleb Ali, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Thiazolidinone derivatives : |
| Remainder of title | design, synthesis and biological evaluation as hypoglycemic agents / |
| Statement of responsibility, etc. | by Mona Ahmed Gamal Eldien Teleb Ali ; Supervised Prof. Dr. Ghaneya Sayed Hassan Ibrahim, Prof. Dr. Marwa Ahmed Fouad, Dr. Samar Hashem Fahem. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | مشتقات الثيازوليدينون : |
| Remainder of title | تصميم وتشييد و تقييم نشاطها كمخفضات لمستوى السكر في الدم / |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2024. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 139 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 116-139. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides IIIa-l and IVa-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities. Compounds IIId and IIIe showed potent inhibitory activities (IC50= 0.440 and 0.3456 µM), comparable with that of the positive control (acarbose 17; IC50=0.420 μM). All the synthesized derivatives were also tested for their inhibitory activities against hCA I, II, IX, and XII. They exhibited different levels of inhibition against these isoforms. Compound IIId outstood as the most potent one against hCA II with Ki equals to 7.0 nM, more potent than the reference standard (acetazolamide; Ki=12.0 nM). In silico studies for the most active compounds within the active sites of α-glucosidase and hCA II revealed good binding modes that can explain their biological activities. MM-GBSA refinements and molecular dynamic simulations were performed on the top-ranking docking pose of the most potent compound IIId to confirm the formation of stable complex with both targets. Compound IIId was screened for its in vivo antihyperglycemic efficacy by using the oral glucose tolerance test. Compound IIId decreased blood glucose level to 217 mg/dl, better than the standard acarbose 17 (234 mg/dl). Hence, this suggests its synergistic mode of action on post prandial hyperglycemia and hepatic gluconeogenesis. Thus, these benzenesulfonamide thiazolidinone hybrids could be considered as promising multi-target candidates for the treatment of type II diabetes mellitus.<br/> Additionally, elevated level of aldose reductase 2 (ALR2) in hyperglycemic conditions activates the polyol pathway and leads to the abnormal buildup of sorbitol. This overabundance of sorbitol in insulin-resistant tissues leads to the development of many diabetes complications. Consequently, the inhibition of aldose reductase 2 has been recognized as a feasible approach for tackling diabetic complications. This work involves design and synthesis of new thiazolidinone IXa-l, Xa-e and thiazoline XIIa-f congeners as potential ALR2 inhibitors. Most of the compounds revealed potent ALR2 inhibitory activity with IC50 spanning from 0.112 to 5.836 µM. The thiazolidinone derivative IXf with a lipophilic p-chloro substituent showed the highest inhibitory activity with IC50 value of 0.112 μM comparable to epalrestat (IC50 = 0.137 µM). Of special interest, the thiazoline derivative XIId showed excellent inhibitory activity with IC50 = 0.134 µM. Compound IXf significantly reduced the blood glucose level in vivo by 52.84% comparable to glibenclamide (64.10%). The kinetic study stated that compound IXf inhibited the enzyme in a mixed competitive and noncompetitive manner. ADME and physicochemical properties prediction indicated a preference for drug absorption compared to epalrestat (acidic carboxylic group) at the physiological pH due to usage of the non-acidic carboxamide group. Finally, molecular docking studies were in agreement with the results of the kinetic study revealing the same binding pattern as the co-crystallized ligand: tolrestat, and the reference drug: epalrestat. Therefore, these congeners could be considered promising candidates for inhibition of ALR2 and treatment of diabetic complications. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | داء السكري هو اضطراب مزمن لوظائف لعدد من الإنزيمات الرئيسية التي يمكن اعتبارها أهدافا لتصميم الأدوية المضادة للسكري. هذه الدراسة تهدف الي التصميم والتوليف والتقييم البيولوجي لسلسلتين من السلفوناميدات القائمة على ثيازوليدينون IIIa-l و IVa-c كروابط موجهة متعددة الأهداف مع نشاط محتمل مضاد للسكري من خلال استهداف الإنزيمات: الفا جلوكوسيداز و الكربونيك انهيدراز البشري . تم تقييم السلفوناميدات المركبة لنشاطها المثبط ضد الفا جلوكوسيداز حيث أظهرت معظم المركبات أنشطة جيدة إلى قوية. أظهر المركبان IIId و IIIe أنشطة مثبطة قوية (0.440 و 0.3456 ميكرومتر) ، قابلة للمقارنة مع الاكاربوز (0.420 ميكرومتر). صمد المركب IIId باعتباره الأقوى ضد hCA II مع Ki يساوي 7.0 نانومتر ، أقوى من أسيتازولاميد = 12.0 نانومتر).كما خفض المركب IIId مستوى الجلوكوز في الدم إلى 217 مجم / ديسيلتر ، أفضل من الأكاربوز (234 مجم / ديسيلتر). تم إجراء المحاكاة الديناميكية على وضع الالتحام الأعلى تصنيفًا للمركب الأكثر فعالية IIId من أجل تقييم تأثير جزيئات الماء على التحام المركب بالانزيم. في دراسات السيليكو للمركبات الأكثر نشاطا داخل المواقع النشطة ل الفا جلوكوسيداز و الكربونيك انهيدراز كشفت عن أنماط ربط جيدة يمكن أن تفسر أنشطتها البيولوجية. يتضمن هذا العمل أيضا تصميم وتوليف مركبات ثيازوليدينون IXa-l و Xa-e و الثيازولين XIIa-f الجديدة كمثبطات الالدوز المختزل. كشفت معظم المركبات عن نشاط مثبط قوي ل الالدوز المختزل مع IC50 يمتد من 0.112 إلى 5.836 ميكرومتر. أظهر مشتق الثيازوليدينون IXf مع أعلى نشاط مثبط بقيمة IC50 تبلغ 0.112 ميكرومتر مقارنة ب الايبلريستات (0.137 ميكرومتر). كما أظهر مشتق الثيازولين XIId نشاطا مثبطا ممتازا( 0.134 ميكرومتر(. خفض المركب IXf بشكل كبير مستوى الجلوكوز في الدم في الجسم بنسبة 52.84٪ مقارنة بغليبينكلاميد (64.10٪). ذكرت الدراسة الحركية أن المركب IXf يثبط الإنزيم بطريقة تنافسية وغير تنافسية. أشار التنبؤ بالخواص الفيزيائية والكيميائية إلى تفضيل امتصاص الدواء مقارنة ب الإيبالريستات (المجموعة الكربوكسيلية الحمضية) بسبب استخدام مجموعة الكربوكساميد غير الحمضية. أخيرا ، كانت دراسات الالتحام الجزيئي متفقة مع نتائج الدراسة الحركية التي كشفت عن نفس نمط الارتباط بال الإيبالريستات و التولريستات. |
| 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 | Thiazolidinone |
| -- | α-glucosidase |
| -- | Carbonic anhydrase |
| -- | molecular dynamics |
| -- | aldose reductase 2 |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ghaneya Sayed Hassan Ibrahim |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Marwa Ahmed Fouad |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Samar Hashem Fahem |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2024 |
| Supervisory body | Ghaneya Sayed Hassan Ibrahim |
| -- | Marwa Ahmed Fouad |
| -- | Samar Hashem Fahem |
| 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 | 08.04.2025 | 90850 | Cai01.08.05.Ph.D.2024.Mo.T | 01010110090850000 | 08.04.2025 | 08.04.2025 | Thesis |