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Antimycobacterial isosters of salicylanilides
Matyk, Josef ; Waisser, Karel (advisor) ; Čižmárik, Jozef (referee) ; Lešetický, Ladislav (referee)
V PhD disertaci byla popsána skupina 79 látek (4-alkylfenyl)salicylamidů, N-heteroarylsalicylamidů, 3-(4-alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)-dionů, 3- (4-alkylfenyl)-2H-1,3-bemzoxazin-4(3H)thioxo-2-onů, 3-(4-alkylfenyl)-2H-1,3- benzoxazin-2,4(3H)-dithionů a 3-heteroaryl-2H-1,3-benzoxazin-2,4(3H)-dionů. Látky byly hodnoceny na antimykobakteriální, antifungální a antibakteriální aktivitu. Vybrané látky byly hodnoceny na cytotoxicitu. Deriváty (4-alkylfenyl)salicylamidů byly analyzovány přístupem QSAR (Kvantitativní vztahy mezi strukturou a aktivitou) a to metodou podle Freeho a Wilsona. Struktura připravených látek byla ověřena 1 H-NMR a IČ-spektroskopií a jejich čistota elementární analýzou. Deriváty (4-alkylfenyl)salicylamidů, N-heteroarylsalicylamidů, 3-(4- alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)-dionů, 3-(4-alkylfenyl)-2H-1,3- bemzoxazin-4(3H)thioxo-2-onů, 3-(4-alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)- dithionů a 3-heteroaryl-2H-1,3-benzoxazin-2,4(3H)-dionů vykazovaly vysokou aktivitu vůči Mycobacsterium tuberculosis a atypickým kmenům mykobaktérií (M. avium a M. kansdasii).
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New groups of potential antibuberculotics
Adamec, Jan ; Waisser, Karel (advisor) ; Lešetický, Ladislav (referee) ; Čižmárik, Jozef (referee)
9. Summary This work is focused on the synthesis and biological evaluation of the derivatives of 1-aryl-5-(benzylsulphanyl)tetrazole and group of hybrid molecules of estrone. It has been found before that alkylsulphanyl group bound to an electron deficient carbon of heterocyclic system represents a pharmacophore responsible for a significant antimycobacterial activity. It has been reported that some antimycobacterial compounds are often antifungal as well. The study is subdivided into three parts. The first one compares the antimycobacterial activity of a group of derivatives of 1-aryl-5-(alkylsulphanyl)tetrazole derivatives (where ethyl, propyl, iso-propyl or allyl stands for the alkyl) and 1-aryl-5-(benzylsulphanyl)tetrazole. The benzyl derivatives exhibited significantly better activity, which was further confirmed by the QSAR analysis. Concerning the group of benzyl derivatives, it was observed that, substitution on the benzyl moiety leads to lower activity. The second studied subject was the antifungal activity of the prepared 1-aryl-5-(benzylsulphanyl)tetrazoles evaluated on eight clinically important fungal strains. The activity was negligible with the exception of Trichophyton mentagrophytes. By means of QSAR analysis, it was found out in the studied group that the increase in the lipophility causes...
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Antimycobacterial isosters of salicylanilides
Matyk, Josef ; Waisser, Karel (advisor) ; Čižmárik, Jozef (referee) ; Lešetický, Ladislav (referee)
V PhD disertaci byla popsána skupina 79 látek (4-alkylfenyl)salicylamidů, N-heteroarylsalicylamidů, 3-(4-alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)-dionů, 3- (4-alkylfenyl)-2H-1,3-bemzoxazin-4(3H)thioxo-2-onů, 3-(4-alkylfenyl)-2H-1,3- benzoxazin-2,4(3H)-dithionů a 3-heteroaryl-2H-1,3-benzoxazin-2,4(3H)-dionů. Látky byly hodnoceny na antimykobakteriální, antifungální a antibakteriální aktivitu. Vybrané látky byly hodnoceny na cytotoxicitu. Deriváty (4-alkylfenyl)salicylamidů byly analyzovány přístupem QSAR (Kvantitativní vztahy mezi strukturou a aktivitou) a to metodou podle Freeho a Wilsona. Struktura připravených látek byla ověřena 1 H-NMR a IČ-spektroskopií a jejich čistota elementární analýzou. Deriváty (4-alkylfenyl)salicylamidů, N-heteroarylsalicylamidů, 3-(4- alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)-dionů, 3-(4-alkylfenyl)-2H-1,3- bemzoxazin-4(3H)thioxo-2-onů, 3-(4-alkylfenyl)-2H-1,3-benzoxazin-2,4(3H)- dithionů a 3-heteroaryl-2H-1,3-benzoxazin-2,4(3H)-dionů vykazovaly vysokou aktivitu vůči Mycobacsterium tuberculosis a atypickým kmenům mykobaktérií (M. avium a M. kansdasii).
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Chalcones and their analogues as potential drugs.
Chlupáčová, Marta ; Hartl, Jiří (advisor) ; Kuneš, Jiří (referee) ; Čižmárik, Jozef (referee)
1 SUMMARY This dissertation thesis deals with searching for potential drugs, particularly with preparation and biological activity study of natural compounds derivatives - chalcones. The work includes preparation of intermediates - 5-alkylated pyrazin-2-carbonitriles and 1-pyrazinyl-2-ethanones. Substituted chalcones, several series of pyrazine analogues of chalcones and Michael adducts of chalcones with different thiols were prepared as final products. In this part of the work, known reaction methodologies were used. Products were identified by melting point, resp. boiling point, IR, NMR spectra. Their purity was checked by elemental analysis. In the case of liquids, elemental analysis could not be performed, and MS spectra were recorded instead. In total were prepared 22 intermediates (9 of them have been described in our department) 62 final products (19 of them have been already described) 1 by-product 57 Unknown compounds were prepared. Synthesis of 12 compounds was not successful. The final products were tested for their antimycobacterial, antifungal, antialgal, and antiaggregating effects. The chalcones were examined for the ability to inhibit one of the cysteine protease - papain and this part of the work continued in a preliminary kinetic study of reaction addition of chalcones with thiol-...
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