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Synthesis and Biological Activity of Dihydroxybenzoic Acids Derivates
Skála, Pavel ; Macháček, Miloš (advisor) ; Pytela, Oldřich (referee) ; Doležal, Martin (referee)
The dissertation focuses on such derivatives of dihydroxybenzoic acids which can be considered to be derived from salicylic acid. The prepared substances were evaluated for their antimycobacterial and antifungal activity in vitro. The work on the dissertation produced 102 compounds, including 72 original ones. The prepared initial compounds included four series of dihydroxy-N- phenylbenzamides, in which one hydroxy group is in position 2 and the position of the second one is successively changed. Their thionation using the patented method developed by our laboratory produced the corresponding dihydroxy-N-phenylthiobenzamides. The cyclization reaction of the initial dihydroxy-N-phenylbenzamides with methyl-chloroformate yielded four series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones with hydroxy groups in positions 8, 7, 6, and 5. Direct melting of prepared 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones with Lawesson's reagent provided the expected products, 3-phenyl-4-thioxo-3,4-dihydro-2H- 1,3-benzoxazin-2-ones and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones, but only in the series of 5-hydroxy derivatives. It was the reason for a search for other methods for the preparation of thionated derivatives of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dione. The highest antifungal activities were exerted by...
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Heterocyclic Compounds with Antimycobacterial Activity
Herzigová, Petra ; Klimešová, Věra (advisor) ; Potáček, Milan (referee) ; Pytela, Oldřich (referee)
The dissertation thesis belongs to the conception of the research of potential antimycobacterial compounds. The aim of this work is synthesis of sulphide pyridine derivatives and the relationship between structure and antimycobacterial activity. Within the framework of this Thesis, the 112 substituted derivates of 4-(subst. fenylalkylsulfanyl)pyridine-2-carboxylic acid were synthesized. Antimycobacterial activity of prepared substances has been tested under in vitro conditions against M. tuberculosis, and non-tuberculous mycobacteria M. avium and M. kansasii. The series of 4-(subst. phenethylsulfanyl)pyridine-2-carbothioamide (MIC 1-32 µmol/L) represents the most active substances (MIC 1-32 µmol/L). These derivates don't reach the activity used antituberculosis drugs against M. tuberculosis, but their activities against M. avium exceed that of isoniazid. The synthesis of new structures as potential antimycobacterial compounds forms the second part of Thesis. All synthesis is based on the use of bis- arylimidoyl chlorides of oxalic acid of as starting material. None of prepared new compounds don't display an interesting antimycobacterial activity.
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Synthesis and Biological Activity of Dihydroxybenzoic Acids Derivates
Skála, Pavel ; Macháček, Miloš (advisor) ; Pytela, Oldřich (referee) ; Doležal, Martin (referee)
The dissertation focuses on such derivatives of dihydroxybenzoic acids which can be considered to be derived from salicylic acid. The prepared substances were evaluated for their antimycobacterial and antifungal activity in vitro. The work on the dissertation produced 102 compounds, including 72 original ones. The prepared initial compounds included four series of dihydroxy-N- phenylbenzamides, in which one hydroxy group is in position 2 and the position of the second one is successively changed. Their thionation using the patented method developed by our laboratory produced the corresponding dihydroxy-N-phenylthiobenzamides. The cyclization reaction of the initial dihydroxy-N-phenylbenzamides with methyl-chloroformate yielded four series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones with hydroxy groups in positions 8, 7, 6, and 5. Direct melting of prepared 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones with Lawesson's reagent provided the expected products, 3-phenyl-4-thioxo-3,4-dihydro-2H- 1,3-benzoxazin-2-ones and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones, but only in the series of 5-hydroxy derivatives. It was the reason for a search for other methods for the preparation of thionated derivatives of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dione. The highest antifungal activities were exerted by...
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Heterocyclic Compounds with Antimycobacterial Activity
Herzigová, Petra ; Klimešová, Věra (advisor) ; Potáček, Milan (referee) ; Pytela, Oldřich (referee)
The dissertation thesis belongs to the conception of the research of potential antimycobacterial compounds. The aim of this work is synthesis of sulphide pyridine derivatives and the relationship between structure and antimycobacterial activity. Within the framework of this Thesis, the 112 substituted derivates of 4-(subst. fenylalkylsulfanyl)pyridine-2-carboxylic acid were synthesized. Antimycobacterial activity of prepared substances has been tested under in vitro conditions against M. tuberculosis, and non-tuberculous mycobacteria M. avium and M. kansasii. The series of 4-(subst. phenethylsulfanyl)pyridine-2-carbothioamide (MIC 1-32 µmol/L) represents the most active substances (MIC 1-32 µmol/L). These derivates don't reach the activity used antituberculosis drugs against M. tuberculosis, but their activities against M. avium exceed that of isoniazid. The synthesis of new structures as potential antimycobacterial compounds forms the second part of Thesis. All synthesis is based on the use of bis- arylimidoyl chlorides of oxalic acid of as starting material. None of prepared new compounds don't display an interesting antimycobacterial activity.
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