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Synthesis of substituted arylguanidines as potential drugs XIII.
Straka, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles university Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Ondřej Straka Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XIII. The ever increasing number of bacterial strains resistant to the currently used antibiotics intensifies the demand for new structures with antibacterial activity. Similarly, the high mortality of immunocompromised individuals caused by pathogenic fungi requires the synthesis of new drugs with antifungal activity. At the Department of Organic and Bioorganic Chemistry, the Faculty of Pharmacy, Charles University has been studying for many years with the potential antifungal and antibacterial activity of arylguanidins, which has been linked to this work. Two series of derivatives of arylguanidines, totaling seven substances in four-step synthesis were synthesized in the thesis. In the first step, a sulfide was formed by the reaction of substituted chloronitrobenzene and thiol. The nitro group was reduced to the amino group in the next step. The aniline formed was converted to anilinium chloride using gaseous hydrogen chloride. At the last step of the synthesis, anilinium chloride reacted with cyanamide to form arylguanidine. Antifungal and...
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Synthesis of substituted arylguanidines as potential drugs X.
Jarešová, Dominika ; Palát, Karel (advisor) ; Vinšová, Jarmila (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Author: Dominika Jarešová Supervisor: PharmDr. Karel Palát, CSc. Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs X. The increasing frequency of diseases caused by tuberculosis and pathogenic fungi leads to high mortality especially of immunocompromised patients. Therefore it is necessary to find new substances with anti-mycobacterial and antifungal activity. Series of on the ring substituted phenylguanidines were synthetized in this diploma thesis, specifically [5-methyl-(2-tetradecylsulfanyl)phenyl]guanidines with the change of substituents on guanidine group and 1,1-dimethyl-3-[4-(pentadecylsulfanyl)fenyl] guanidine. The oxidation of [(4-oktylsulfany)fenyl]guanidinium-nitrate was done. Substances were tested against series of pathogenic fungi and genus Mycobacterium. Products were synthetized in the four-step synthesis. Alkylarylsulfides were prepared by the reaction between alkylthiols and 4-chloro-3-nitrotoluene or p-chloronitrobenzene with active copper as a catalyst in the first step. The nitro group on the ring was reduced to amino group by the reaction with stannous chloride under nitrogen atmosphere in the second step. Sulfanylphenylamines were then...
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Synthesis of 5-hydroxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and their sulfur
Růžková, Barbora ; Macháček, Miloš (advisor) ; Palát, Karel (referee)
Synthesis of 5-hydroxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and their sulfur analogues Barbora Růžková The thesis is concerned with the preparation of 5-hydroxy-3-phenyl-2H-1,3-benzoxazine- 2,4(3H)-diones, 5-hydroxy-3-phenyl-4-thioxo-2H-1,3-benzoxazin-2-ones and 5-hydroxy-3- phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones, i.e. cyclic analogues of 2,6-di- hydroxybenzanilides. The starting 2,6-dihydroxybenzanilides were synthesized by the microwave-assisted reaction of 2,6-dihydroxybenzooic acid with aniline (unsubstituted or para-substituted by chlorine, methyl, butyl or methoxy groups) in the presence of phosphorus trichloride. Their treatment with ethyl-chloroformate afforded 5-hydroxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)- diones in 77 - 94 % yields. 5-Hydroxy-3-phenyl-4-thioxo-2H-1,3-benzoxazin-2-ones and 5- hydroxy-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones were obtained by thionation using Lawesson's reagent in 31 - 42 and 24 - 33 % yields, respectively. All the compounds were characterized by infrared and NMR spectroscopy and by elemental analysis. No substance exerted either antimycotic activity (against Candida albicans, C. tropicalis, C. krusei, C. glabrata, Trichosporon asahii, Trichophyton mentagrophytes, Aspergillus fumigates, and Absidia corymbifera) or antimycobacterial activity...
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Synthesis of substituted arylguanidines as potential drugs XVI.
Gyurkovicsová, Eszter ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic chemistry Student: Eszter Gyurkovicsová Supervisor: PharmDr. Karel Palát, CSc. Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XVI. Continually increasing number of systemic mycosis and the genesis of new diseases caused by fungi resistant to existing antifungal drugs is a huge problem in protecting human health. Around 1,2 billion individuals worldwide suffer from fungal infections. Primarily patients with insufficient immune function [1] are at risk, their number is growing as a result of the spread of HIV infection or intensive cancer therapy, in conditions after organ transplants or suffering from autoimmune diseases that require immunosuppressive therapy. Research is in progress worldwide on guanidine-derived substances with potential activity against many strains of fungi and bacteria. The Faculty of Pharmacy in Hradec Králové has also been researching these substances for several years. The aim is to obtain the most active compounds of substituted arylguanidines in an effort to find the structure-activity relationship for these substances. In my thesis, two series of arylguanidine derivatives were synthesized. The products were synthesized in a four-step...
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Synthesis of substituted arylguanidines as potential drugs XV.
Brezinová, Katarína ; Palát, Karel (advisor) ; Matouš, Petr (referee)
Katarína Brezinová Synthesis of substitued arylguanidines as potential drugs XV Diploma thesis Charles University, Faculty of pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry PharmDr. Karel Palát, CSc. Hradec Králové,2021 Antimicrobial and antifungal resistance are terms that are very often used today. The increase in bacterial strains resistant to the antibiotics used is alarming, as is the increase in resistance in pathogens causing mycotic diseases. The increasing state of resistance requires the synthesis of new substances with antifungal and antibacterial activity. Two different 1,1-dimethyl -2-[3-methyl-4-(alkylsulfanyl)phenyl]guanidinium derivatives, two different 2-[3-methyl-4-(alkylsulfanyl)phenyl]guanidinium nitrates, which differed in alkyl chain length, were synthesized in the thesis work. These substances were sent for antibacterial tests to the Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Hradec Kralove . The substances showed antibacterial and antifungal activity against several bacterial pathogens comparable to or better than the standards used. The substance 1,1-dimethyl -2-[5-methyl-2-(decylsulfanyl)phenyl]guanidine was also synthesized, which complements a series of substances synthesized in previous years. A...
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Synthesis of substituted arylguanidines as potential drugs XIII.
Straka, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles university Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Ondřej Straka Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XIII. The ever increasing number of bacterial strains resistant to the currently used antibiotics intensifies the demand for new structures with antibacterial activity. Similarly, the high mortality of immunocompromised individuals caused by pathogenic fungi requires the synthesis of new drugs with antifungal activity. At the Department of Organic and Bioorganic Chemistry, the Faculty of Pharmacy, Charles University has been studying for many years with the potential antifungal and antibacterial activity of arylguanidins, which has been linked to this work. Two series of derivatives of arylguanidines, totaling seven substances in four-step synthesis were synthesized in the thesis. In the first step, a sulfide was formed by the reaction of substituted chloronitrobenzene and thiol. The nitro group was reduced to the amino group in the next step. The aniline formed was converted to anilinium chloride using gaseous hydrogen chloride. At the last step of the synthesis, anilinium chloride reacted with cyanamide to form arylguanidine. Antifungal and...
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Synthesis and evaluation of potential cholinesterases inhibitors
Vu, Quynh Anh ; Krátký, Martin (advisor) ; Palát, Karel (referee)
This bachelor thesis deals with the synthesis of novel acetylcholinesterase and butyrylcholinesterase inhibitors as potential inhibitors of both cholinesterases. All the prepared molecules contain propargylamine structural motif, i.e., a proved scaffold for drugs targeting central nervous system. Some of its derivatives are currently investigated for the treatment of neurodegenerative disorders including Alzheimer's disease. The theoretical part summarizes facts about the Alzheimer's disease and its current treatment focused on cholinergic hypothesis and inhibitors of cholinesterases. The experimental part reports the synthesis and evaluation of potential inhibitors of acetylcholinesterase and butyrylcholinesterase. Seventeen compounds were synthesized in satisfactory yields, predominantly amides and imines of salicylic and cinnamic acid derivatives. All of them were investigated for their activities against both cholinesterases using Ellman's method. 5-Bromo-N-(prop-2-yn-1-yl)salicylamide and N-(prop-2-yn-1- yl)benzamide showed the lowest IC50 values for acetylcholinesterase (8.05 and 23.16 µM, respectively). 2,4-Dibromo-6-[(prop-2-yn-1-yl)carbamoyl]phenyl (N-ethyl-N- methyl)carbamate showed the best inhibition of butyrylcholinesterase (IC50 = 26.09 µM). Several of the prepared compounds were more...
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Synthesis of substituted arylguanidines as potential drugs XIII.
Straka, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles university Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Ondřej Straka Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XIII. The ever increasing number of bacterial strains resistant to the currently used antibiotics intensifies the demand for new structures with antibacterial activity. Similarly, the high mortality of immunocompromised individuals caused by pathogenic fungi requires the synthesis of new drugs with antifungal activity. At the Department of Organic and Bioorganic Chemistry, the Faculty of Pharmacy, Charles University has been studying for many years with the potential antifungal and antibacterial activity of arylguanidins, which has been linked to this work. Two series of derivatives of arylguanidines, totaling seven substances in four-step synthesis were synthesized in the thesis. In the first step, a sulfide was formed by the reaction of substituted chloronitrobenzene and thiol. The nitro group was reduced to the amino group in the next step. The aniline formed was converted to anilinium chloride using gaseous hydrogen chloride. At the last step of the synthesis, anilinium chloride reacted with cyanamide to form arylguanidine. Antifungal and...
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Study of substituted arylguanidines as potential drugs XIV.
Kobosilová, Jana ; Palát, Karel (advisor) ; Kováčik, Andrej (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Jana Kobosilová Supervisor: PharmDr. Karel Palát, CSc. Title of bachelor thesis: Study of substitued arylguanidines as potencial drugs XIV. In view of the increasing number of fungal pathogens and the increased resistance of these pathogens to already available antifungal agents, a new structure inhibiting the growth of these pathogens must be sought. In the area of guanidine-derived substances, a worldwide research is taking place, which is also attended by the Faculty of Pharmacy in Hradec Králové. As part of my bachelor thesis, five previously unpublished substances have been synthesized: hexadecyl(4-methyl-2-nitrophenyl) sulfide 2-(hexadecylsulfanyl)-5-methylaniline 2-(hexadecylsulfanyl)-5-methylanilinium chloride 2-[2-(hexadecylsulfanyl)-5-methylphenyl]guanidinium nitrate 2-[2-(hexadecylsulfanyl)-5-methylphenyl]-1,1-dimethylguanidine
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Synthesis of substituted arylguanidines as potential drugs XIII.
Straka, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles university Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Ondřej Straka Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XIII. The ever increasing number of bacterial strains resistant to the currently used antibiotics intensifies the demand for new structures with antibacterial activity. Similarly, the high mortality of immunocompromised individuals caused by pathogenic fungi requires the synthesis of new drugs with antifungal activity. At the Department of Organic and Bioorganic Chemistry, the Faculty of Pharmacy, Charles University has been studying for many years with the potential antifungal and antibacterial activity of arylguanidins, which has been linked to this work. Two series of derivatives of arylguanidines, totaling seven substances in four-step synthesis were synthesized in the thesis. In the first step, a sulfide was formed by the reaction of substituted chloronitrobenzene and thiol. The nitro group was reduced to the amino group in the next step. The aniline formed was converted to anilinium chloride using gaseous hydrogen chloride. At the last step of the synthesis, anilinium chloride reacted with cyanamide to form arylguanidine. Antifungal and...
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