Farmakološko djelovanje i primjena izatina i izatinskih derivata

master's thesis

• Title (english): Pharmacological activity and application of isatin and isatin derivatives
• Author: Petra Bulat
• Mentor: Petra Turčić (mentor)
• Committee member: Petra Turčić (predsjednik povjerenstva)
• Committee member: Željan Maleš (član povjerenstva)
• Committee member: Ivana Perković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2023-06-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Izatin je prirodni alkaloid narančaste boje izoliran iz biljaka roda Isatis prisutnih po cijelom svijetu. O.L. Erdman i A. Laurent prvi su puta 1841. godine sinetizirali izatin oksidacijom indiga smjesom dušične i kromne kiseline, a do danas je otkriven velik broj izatinskih derivata od kojih su neki pokazali značajna antitumorska, antibakterijska, antikonvulzivna, protuupalna i brojna druga djelovanja. Iako izatinski derivati imaju širok spektar djelovanja, do sada se antitumorsko djelovanje pokazalo najznačanijim. Sunitinib je derivat izatina koji je 2006. godine registrirala EMA u liječenju GIST-a, a kasnije i za liječenje neoperabilnih ili metastatski dobro diferenciranih tumora gušterače (pNET) i metastatskog karcinoma bubrežnih stanica (MRCC). Osim što je registriran kao lijek u navedenim indikacijama, sunitinib prolazi kroz klinička ispitivanja kao dvojna terapija s docetakselom, kapecitabinom i paklitakselom. Inhibitor je više tirozin kinaza te tako sprječava rast tumora, proliferaciju stanica i angiogenezu, a značajno inhibitorno djelovanje pokazao je prema VEGFR i PDGFR. Indirubin je poznat izatinski derivat s protuupalnim, antiproliferativnim, hepatoprotektivnim i protuleukemijskim djelovanjem. Iako njegova sigurnost i učinkovitost nije dokazana, u tradicionalnoj se kineskoj medicini koristi u terapiji psorijaze, prevenciji mastitisa uzrokovanog LPS-om E. Coli i S. aureus te kao dodatna terapija CML-a. Hibridi izatinskih derivata s fluorokinolonima ispituju se kao antibakterijska terapija u liječenju infekcija uzrokovanih H. influenzae, K. pneumonia, P.aeruginosa. U najnovijim istraživanjima pronađeno je da djelovanjem bakterijskih enzima u crijevima dolazi do sinteze izatina iz triptofana što uzrokuje povećane koncentracije izatina u tjelesnim tekućinama i mozgu. Do navedene promjene dolazi tijekom izloženosti akutnom stresu, tijekom Parkinsonove bolesti zbog povećanog broja bakterija roda Enterococcaceae te se često javlja kod pacijenata oboljelih od bulimije. Ovim diplomskim radom prikazana su najistaknutija farmakološka djelovanja izatina i izatinskih derivata i učinak bakterijske mikroflore na rad i funkciju mozga.

Abstract (english)

Isatin is natural alkaloid, isolated as orange solid from plants of Isatis genus. First synthesis of isatin dates back to 1841. when O.L. Erdman and A. Laurent obtained it by oxidation of indigo with mixture of nitric and chromic acid. Up to now, large number of isatin derivatives with various pharmacological activities, some of which are antibacterial, antitumor, anticonvulsant, anti-inflammatory etc., have been reported. Isatin derivatives as antitumor agents have been mostly studied and Sunitinib is the one of isatin derivatives which EMA registrated in 2006. for treatment of GIST, pNet's and MRCC. At the moment, Sunitinib is in the clinical trial in combination with capecitabine, paclitaxel and docetaxel in treatment for the different types of tumours. It is multi-tyrosine receptor kinase inhibitor and therefore it prevents growth and proliferation of tumors cells and angiogenesis. Significant inhibitory activity has been reported with VEGFR and PDGFR. Indirubin is isatin derivative with anti-inflammatory, antiproliferative, hepatoprotective and antileukemic activity. Although it's safety and efficiency are not proven, in Chinese traditional medicine it is used in treatment of psoriasis, mastitis caused by E. Coli and S. aureus prevention and as additional therapy of the CML. Isatin hybrids of fluoroquinolones show antibacterial activity to H. influenze, K. pneumonie, P. aerugionosa and many others. Recent studies reported that isatin can be synthesized from triptofan by gastrointestinal bacterial enzymes which leads to high isatin concentarion in body fluids and brain. This is often caused by acute stress, large number of Enterococcaceae in patient with Parkinson disease and bulimia. This review shows the most prominent pharmacological effect of isatin and isatin derivatives and the effect of bacterial microflora on activity and function of brain.

• Keywords: izatin; izatinski derivati; sunitinib; antitumorsko djelovanje; angiogeneza; indirubin; antibakterijsko; protuupalno djelovanje
• Keywords (english): isatin; isatin derivatives; sunitinib; antitumor agents; angiogenesis; indirubin; antibacterial; anti-inflammatory
• Language: croatian
• URN:NBN: urn:nbn:hr:163:359861
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-06-27
• Created on: 2024-01-26 14:06:32