"Department of Organic Chemistry, Faculty of Natural Sciences, Komenský University, CS Bratislava

Transcription

1 Benthiale cpns. Synthesis f 3 an 2,3sbstitte benthiali salts, investigatin f their antiicrbial an grwthregláting activity "V. SUTORS, a J. HALGAŠ, b P. FOLTÍNOVÁ, an C V SEKERKA "Departent f Organic Cheistry, Faclty f Natral Sciences, Kenský University, CS Bratislava ь nstitte f Mleclar an Sbcelllar Bilgy, Kenský University, CS Bratislava c Departent f Mleclar Bilgy an Genetics, Faclty f Natral Sciences, Kenský University, CS Bratislava Receive 15 Febrary Sbstitte an 2,3isbstitte benthiali salts were prepare by treatent f benthiale r 2akylbenthiales with reactive halies r ialkyl slfates. The antibacterial, antifngal, an antiprtal activity f the salts is reprte. 3Ethyl, 3prpy, an 3btylbenthiali salts were fn t be active against sch strains f Staphylcccs ares which are resistant t se antibitics. Several cpns shwe g grwth stilating an/r inhibiting activity. ЗЗамещенные и 2,3дизамещенные соли бензотиазола были получены действием на бензотиазол или 2алкилбензотиазолы реакционными галогенидами или диалкил сульфатами. Сообщается о антибактериальной, антигрибковой и антипротозойной активности этих солей. ЗЭтил, 3пропил и 3бутилбензотиазолиевые соли оказались активными по отношению к таким штаммам Staphylcccs ares, которые резистентны к некоторым антибиотикам. Некоторые соединения проявили хорошую ростстимулирующую или ингибирующую активность. Or previs reslts [1 3] f investigatins int grwthreglating an antiicrbial prperties f benthiali salts encrage s t synthesiing re erivatives f this type. The effects f sbstitents in psitins 2 an 3 n bilgical activity were stie. 3Sbstitte an 2,3isbstitte benthiali salts given in Table 1 were prepare, like previs series f cpns f this type [1 3], by treatent f benthiale, 2ethyl r 2prpylbenthiale with Che. vestí 38 (2) (1984) 247

2 V. SUTORS, J. HALGAŠ, P. FOLTÍNOVÁ, V. SEKERKA. 2 «1 (N со «O ^ 1» T со ю»» T t^ i Tf 7 r r O 1^ O Tt r^ wj r» *i «О О *н ii TJri H «O ^ O Ov^vprncnvqjiHO ONr(THiiii OOOOvtHi«" s «5 об i^ in *н i t i rt * < íh íh ^OOOOOOWÍOOOONH r^ool^w^coijpt^r^qc^io *O»TírriOV'^WlOOONOOOi' h ( N > O l O i O N a \ t n O \ T t O O H l O M n r^t^rop^oovqr;^ Tt Tt,.,. Tt ^ ^ ^ 2 S 13 wj ^ t ŕ n r*» Ov я s* J «5 í NH ON g я M v Г*; r Ä t^ Tf ^ PQ sf n r со 5 ď PQ ô š E Os O a? PQ 8 U K (J 8 Я HH HH Ж МЧ * sq 5 > > s 248 Che. vestí 38 (2) (1984)

3 r Q f Cpn R CA R 1 CH 3 SO 4 C 2 H 5 SO 4 Frla C 10 H 13 NO 4 S 2 H 17 N0 4 S 2 Table 1 (Cntine) M r %C H 'i (calc.)/w, (fn) %H %N %S Yiel % M.p. C и i > N О r 8 ö i V V V V V С 4 Н 9 СН()С2Н 5 СНгСбНз сн 3 сн 3 Oft СН 2 СН = СН 2 CH 3 SO 4 Br C H 14 NS NS NS C 15 H 14 NS C M H 14 NS H 17 N0 4 S 2 NS C 13 BrNS Decpsitin

4 V. SUTORS, J. HALGAŠ, P. FOLTÍNOVÁ, V. SEKERKA reactive halies r ialkyl slfates in iethylfraie acetne (ass rati = 2:1) itre with yiels %. Methyl r prpyl grp in psitin 2 have n sbstantial effect n qaterniatin reactin f nitrgen in psitin 3. The reactin an its yiel epen re n the reactivity f the alkylating agent (Table 1). The reslts f antiicrbial tests f benthiali salts are sarie in Table 2. t is evient that the cpns are active ainly against grapsitive bacterial strains (Staphylcccs ares, Bacills sbtilis). There is little r n activity against granegative strains (Escherichia cli, Psenas aerginsa). Antifngal activity (Micrspr gypse, Trichphytn rbr) is significant ainly with the erivatives V The reaining erivatives are less active against fngi teste. The cpns V are the st active against prtal strain Tritrichnas fets as well. Table 2 Antiicrbial activity f the prepare benthiali salts Cpn Mini inhibitry ant a/(g/isc) Fngicial/fngistatical ass cncentratin p/(g c" 3 ) Prtcial/ prtstatical a cncentratin p/(g c" 3 ) V V V V V V V V V V / /> / /> / /> / /> / / /> /> > / /> > / > > /> > /> > / > / > / > / / / > / > / > / > / > / / /> / > / > / / / > /> /> /> / / / / / /> /> 8/ / / / / / /> / / / / 1. Staphylcccs ares ATCC 6538; 2. Bacills sbtilis ATCC6051; 3. Escherichia cli ATCC9637; 4. Psenas aerginsa ATCC 10145; 5. Micrspr gypse; 6. Trichphytn rbr; 7. Tritrichnas fets. 2 Che. vesti 38 (2) (1984)

5 BENZOTHAZOLE MPOUNDS. The erivatives V were teste fr aitinal five strains f Staphylcccs ares, ifferently sensitive t antibitics (Table 3). Stanar antibitical tests were carrie t t check the sensitivity f the strains t antibitics an the reslts are incle in Table 3 fr cparisn. The cpns V were fn t be active als against sch strains f Staphylcccs ares which are rather resistant t antibitics. Hence, after aitinal investigatin, there is pssibility f sing these erivatives fr aking antistaphylcccal preparatins with great avantage f their slbility in water. Table 3 Antibacterial activity f the cpns V an f se antibitics against strains Staphylcccs ares Strain Mini inhibitry ant a/(ng/ isc) Antibitic n V Pn. Er. Tc. K. Cph. Ap. Man 29/58 Man 78/71 CCM 2394 CCM 2560 SPA ± ± Pn. Penicillin 10 i..; Er Erythrycin log/isc; Tc. Tetracycline 30g/isc; K. Kanycin 30 ng/isc; Cph. Chlraphenicl 30 pig/isc; Ap. Aphicillin 20 g/isc. = resistance, = sensitivity, ± = ecrease sensitivity. The reslts f the antiicrbial tests escribe in this paper as well as in the previs nes [1 3] allw t cncle that bth ethyl an prpyl grp in psitin 2 case slightly ecrease activity. Lnger alkyl chains in ester grps (cpns V, V) are nt effective in prting the activity, either. Grwthstilating an inhibiting activity was assesse als in this series f benthiale erivatives. The cpns,, an V were fn t shw better stilating activity than inle3acetic aci r 2,4ichlrphenyacetic aci, which were se as stanars (Table 4). Nticeable inhibiting activity at the cncentratin 10" 3 l " 3 was fn fr the cpns,, V, an V, bt they cannt be regare as typical inhibitrs. Se f the prepare cpns cl be practically se becase f their activity, slbility in water, an siple synthetic availability. Che. vesti 38 (2) (19Й4) 251

6 V. SUTORS, J. HALGAŠ, P. FOLTÍNOVÁ, V. SEKERKA Table 4 Grwthreglating activity f benthiali salts n Via satíva Cpn Al/ Stilatin c/(l 3 ) Al/ nhibitin c/(l " 3 ) V V V V V V V V V V i 7 ю 11 O" 7 O" 7 O" 7 O" 7 O" 11 O" 13 10~ 9 O" 13 O"" O" 7 O" 5 O" 9 O" i 3 O' 3 i 3 AA 2,4D ccc O" 12 O" O" 6 O" 5 AA nle3acetic aci; 2,4D 2,4ichlrphenyacetic aci; CCC 2chlrethyltriethylani chlrie. Eperiental The general prcere fr preparing benthiali salts has been escribe in the paper [1]. Melting pints, yiels, an analytical ata are cntaine in Table 1. Antibacterial activity was easre against bacterial strains Staphylcccs ares ATCC 6538, Bacills sbtilis ATCC 6051, Escherichia cli ATCC 9637, an Psenas aerginsa ATCC by the plate iffsinal eth sing Meller Hint agar with ajstents necessary fr a particlar strain [4]. The cpns were teste at varis ants (a/(g/isc):,,, an 0.78). The reslts are epresse as ants, which case a easrable ne f inhibite bacterial grwth, i.e. ini inhibitry ants. The antibacterial test was 252 Che. vestí 38 (2) (1984)

7 BENZOTHAZOLE MPOUNDS. etene fr Staphylcccs ares strains Man 29/58, Man 78/71, CCM 2394, CCM 2560, an SPA. Stanar cercial antibitical iscs (Lachea, Brn) were se t check the sensitivity f the strains. Antifngal activity against Micrspr gypse an Trichphytn rbr, an antiprtal activity against Tritrichnas fets were eterine by the testtbe iltin eths [5]. Grwthreglating activity was assesse sing seelings f vetch (Vicia sativa) an the eth has been escribe in the previs papers [1, 6]. References 1. Stris, V M Halgaš, J., Sekerka, V., Fltínvá, P., an Gáplvský, A., Che. Zvesti 37,653 (1983). 2. Halgaš, J., Stris, V., Sekerka, V., Fltínvá, P., an Slčánivá, E., Che. Zvesti 37,663 (1983). 3. Halgaš, J., Stris, V., Fltínvá, P., an Sekerka, V., Che. Zvesti 37, 799 (1983). 4. Fltínvá, P. an Blöckinger, G., Bilógia 25, 175 (1970). 5. Fltínvá, P., Stris, V., Blöckinger, G., an Ebringer, L., Flia Micrbil. (Prage) 23, 225 (1978). 6. Stris, V., Sekerka, V., an Halgaš, J., Cech. Appl Translate by J. Halgaš Che. vesfí 38 (2) (1984) 253