|
| |
|
|
New derivatives of combretastatine
Horký, Pavel ; Pour, Milan (advisor) ; Špulák, Marcel (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Pavel Horký Consultant: Prof. RNDr. Milan Pour, Ph.D. Title of Thesis: New derivatives of combretastatine Four 3,4-diaryl-2,5-dihydrofuran-2-ones analogous to cytostatic combretastatines were prepared within this Diploma Thesis. Their preparation was based on the bromination of substituted acetophenones and subsequent esterification of the resultant bromo derivatives with p-bromophenylacetic acid. The esters obtained were subsequently cyclized in an intramolecular aldol process to yield 3,4-diarylfuranones, out of which one compound was further converted to 5-hydroxymethyl and 5,5-bis(hydroxymethyl) derivatives. Two compounds were subjected to screening for cytostatic activity, and evaluated as inactive.
|
|
|
Synthesis and characterisation of flavonoids as potential anticancer agents
Novotný, Lukáš ; Pour, Milan (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry University of Limoges Faculty of Pharmacy Laboratory of Natural Substances Chemistry Consultants: prof. RNDr. Milan Pour, Ph.D., Dr. Christelle Pouget Student: Lukáš Novotný Title of Thesis: Synthesis and characterisation of flavonoids as potential anticancer agents With more than 3 million new cases and 1.7 million deaths each year, cancer represents the second most important cause of morbidity in Europe. Search for new anticancer agents is one of the most important ways to improve treatment and management of cancer. At present, around 50 % of drugs against cancer are natural compounds or have a natural origin. Flavonoids, 2- phenyl-1,4-benzopyrones derivatives, are known for their antioxidant, anti-inflammatory, vasculoprotective, antimicrobial and anticancer properties. This project focuses on flavonoids with open C ring, named chalcones. The synthesis of two original molecules is described: one bichalcone and a combined chalcone-polyamine, prepared for the purpose of screening antiproliferative effect on cancer cell lines. The chalcone derivatives were made using Claisen- Schmidt condensation and Suzuki reaction. Different synthetic approaches are discussed. Presently, the two products are...
|
|
|
Synthesis of substituted pyridines catalyzed by gold complexes
Matouš, Petr ; Pour, Milan (advisor) ; Klimešová, Věra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Petr Matouš Supervisor: Prof. RNDr. Milan Pour, Ph.D. Title of thesis: Synthesis of substituted pyridines catalyzed by gold complexes This work is focused on the synthesis of 3,4-disubstituted pyridine derivatives. MBS-protected propargylamine reacts with methyl propiolate to form 1,5-enyne that undergoes Sonogashira coupling with aryl iodides. Substituted enyne undergoes cyclization to tetrahydropyridine in the presence of tris(2-furanyl)phosphinegold(I)chloride. Deprotection leads to the preparation of substituted pyridines, which could serve as intermediates in organic synthesis or as potential biologically active substances. Keywords: gold catalysis, enyne cyclization, pyridine derivatives
|
|
|
Influence of the protective group on Au(I)-catalyzed cyclisation of 1,5-enynes
Charvát, Martin ; Pour, Milan (advisor) ; Klimešová, Věra (referee)
Within the framework of this Thesis, i have been occupied with optimalization of preparation in position 4 with phenyl substituted methyl ester of nicotinic acid, which was syntetized by gold catalyzed cycloizomerization of 1,5-enyne, which is not commercially available. This optimalized route of synthesis could be applied even for preparation in positions 2,3,4 and 6 substituted derivatives of pyridine.
|
|
|
Anti-adhesive activity of bovine whey oligosaccharides against Neisseria meningitis
Janůšová, Barbora ; Vávrová, Kateřina (advisor) ; Pour, Milan (referee)
RESUME Neisseria meningitidis, je lidský patogen způsobující život ohrožující onemocnění. Tato onemocnění jsou velice závažná a mohou být smrtelná již za několika hodin po manifestaci prvních příznaků. Proto je nezbytně nutná rychlá diagnóza a okamžité nasazení antibiotik. Avšak díky zvýšenému výskytu rezistentních bakteriálních kmenů se stává léčba i prevence velmi obtížná, a jsou tedy hledány nové způsoby terapie. Jedním z nových přístupů může být antiadhesivní terapie využívající glykanů, které zabraňují adhesi bakterií na hostitelské tkáně. Oligosacharidy a glykokonjugáty izolované z kravského a mateřského mléka prokázaly antiadhesivní účinky proti mnoho patogenům, stejně tak i proti N. meningitidis. Tyto komponenty by mohly být tedy využity jako bioaktivní přísada do potravin, a snižovat tak incidenci bakterielních onemocnění. Toto využití je však velmi ekonomicky náročné, a jsou tedy hledány jiné zdroje, které by mohly snížit náklady. Takový zdroj představuje syrovátka vznikající jako odpadní produkt při výrobě sýrů. Cílem této práce tedy bylo izolovat oligosacharidy z kravské syrovátky, separovat je na neutrální a acidické a otestovat jejich antiadhesivní účinky. Pro separaci izolovaných oligosacharidů bylo užito gelové a iontově výměnné chromatografie. Schopnost oligosacharidů zabránit adhesi N....
|
|
|
Synthetic studies on 2,3-disubstituted furan scaffold
Kalina, Jakub ; Špulák, Marcel (advisor) ; Pour, Milan (referee)
There are only few ways leading to 2,3-disubstituted furanes. The aim of my thesis was to optimize method of preparation of these compounds. Two 2,3-disubstituted furanes and one 2,3,5-trisubstituted furane were prepared by palladium catalyzed cyclization of propargyl alkohols with methyl propiolate. All the products were tested for antifungal and antibacterial activity but they did not display any significant effect.
|
|
|
Synthesis of Natural Product Analogues as Potential Antitumour Agents
Voráčová, Manuela ; Pour, Milan (advisor) ; Kuneš, Jiří (referee)
1/2 Abstract Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Manuela Voráčová Supervisors: Prof. RNDr. Milan Pour, PhD Adj. Prof. Paula Kiuru, PhD Title: Synthesis of natural product analogues as potential antitumour agents Keywords: combretastatin, combretafuranone, purpurealidin, cytotoxic, KV10.1 inhibitors, analogue synthesis Despite numerous efforts and advances in prevention, diagnostics and treatment of human malignancies, cancer is still one of the leading causes of mortality worldwide. In the search for novel drug candidates, the rich biodiversity in the nature remains a valuable source of lead structures. Combretastatin A-4 (CA4) isolated from Combretum caffrum tree and purpurealidin I isolated from marine sponge Pseudoceratina purpurea are examples of such structures that served as an inspiration in the synthesis of potential anti-cancer agents within my thesis work. Combretastatin A-4 is a well-known suppressor of tubulin polymerization via interaction with the colchicine binding site. It causes inhibition of cell growth and concurrently acts as a vascular disrupting agent and angiogenesis inhibitor. Being a cis stilbene derivative, it can readily isomerize into a thermodynamically more stable, but less active trans form....
|
|
|
Synthesis of Pyridazines by Ring Transformation Reaction
Budilová, Hana ; Klimešová, Věra (advisor) ; Pour, Milan (referee)
Charles University in Prague The Faculty of Pharmacy in Hradec Králové The Department of Inorganic and Organic Chemistry Candidate: Hana Budilová Supervisors: Doc. RNDr. Věra Klimešová, CSc. Prof. Dr. Rainer Beckert Title of Diploma Thesis: Synthesis of Pyridazines by Ring Transformation Reaction Pyridazines are heterocyclic compounds with two adjacent nitrogen atoms. There are a lot of synthetic approaches to get pyridazine. A number of specific transformations from other heterocyclic systems have been reported. This thesis deals with the synthesis of pyridazines by transformation of a four-membered heterocycle. Some new derivatives of 1-methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-(4'- substituted-phenyl)-1,4-dihydropyridazines were synthesized by a ring transformation of four- membered 2 -1,2-diazetine. This compound was obtained by a cycloacylation reaction of methylhydrazine and bis-oxalimidoyl chloride. NMR and mass spectrometry confirmed structures of prepared compounds. 1-Methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-phenyl-1,4-dihydropyridazine had been previously proven to possess antimycobacterial activity. The new derivatives were tested against Mycobacterium tuberculosis My 331/88, M. avium My 330/88, M. kansasii My 235/80 and M. kansasii 6 509/96. MIC values of these compounds range...
|
|
|
Synthesis of Specifically Substituted Heterocycles via Catalytic Reactions
Kratochvíl, Jiří ; Pour, Milan (advisor) ; Kotora, Martin (referee) ; Dvořák, Dalimil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate Mgr. Jiří Kratochvíl Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis of Specifically Substituted Heterocycles via Catalytic Reactions This Ph.D. thesis deals with the synthesis of γ-alkylidene-α,β-unsaturated δ-lactones and lactams. Migita- Stille cross-coupling served as the key step in their preparation. Catalysis with palladium black was applied to the synthesis of the lactones and we demonstrated that it doesn't act as heterogeneous catalyst. Instead, it's only a precursor for catalytically active species, which is generated in situ and its true nature is unknown. The palladium nanoparticles are most likely responsible for the catalysis, although involvement of complexed atomic palladium cannot be excluded. Palladium black catalysis was also successfully applied to the synthesis of a series of structurally different substrates, which demonstrates its versatility and it was also proved that the catalyst can be easily recycled by simple filtration. An unusual Tsuji-Trost reaction then enabled transfer of the alkylidene substituent of the lactones to C5 furnishing polysubstituted heterocycles.
|
guest ::
RSS feed.