CS261441B1 - Agent with anti-yeast effect - Google Patents

Abstract

Antifungal agent based on 6-nitro-3-(2-alkylthio-6-benzothiazolylaminomethyl)-2-benzothiazolinethione. The agent can be used as an active ingredient in antifungal preparations alone or in a mixture with other substances. Alkyl in the compound is equal to methyl or ethyl.

Description

26I441

An object of the present invention is to provide a composition of the formula having the formula: if c =; ch ^ -nh

z>

N

C- SR wherein R is alkyl of 1 or 2 carbon atoms.

The composition of the present invention has been known to be an antimycobacterial effective agent [Holb, E., Sido, E., and Odler, J., Chem. Rumors 30,709 (1976).

We have now found that the compounds of the general formula are anti-yeast active.

The composition according to the invention is prepared by a mannic reaction from 2-alkylthio-6-amino-benzothiazoles, formaldehyde and 6-nitro-2-benzothiazolinothione (other than 6-nitro-2-mercaptobenzothiazole) in acetone at 35 to 40 degrees C [Holb's , E., Sidó, E., and Odler, J., Chem. Rumors, 30,709 (1976)].

The following examples illustrate, but do not limit, the preparation, properties and use of the composition of the present invention. Example 1 Preparation of 6-nitro-3- (2-methylthio-6-benzothiazol-ylaminomethyl) -2-benzothiazolinothione 6-nitro-2-mercaptobenzotialo (4.24 g, 0.020 mol) is mixed with acetone (300 cm 3). The 2-methylthio-6-aminobenzotialose (3.92 g, 0.020 mol) was added portionwise with stirring, and the mixture was mixed until the amine was dissolved. Thereafter, the solution is heated to 35-40 ° C and a 30% aqueous formaldehyde aqueous solution (2 cm 3, 0.020 mol) is added dropwise at this temperature. After 30 minutes of stirring, the reaction product crystallizes from the solution. After 15 minutes, the mixture stops heating and is allowed to cool to ambient temperature. After 24 hours, the solid was filtered off with suction and washed with acetone (10 cm 3). The yield was 5.88 g (70%): mp 179-181 ° C.

N, 13.32; S, 30.49. Found: C, 45.70; H, 3.01; N, 13.20. S 30.62 Example 2 Preparation of 6-nitro-3- (2-ethylthio-6-benzothiazol-ylaminomethyl) -2-benzothiazolinothione 6-nitro-2-mercaptobenzothiazole (2.12 g, 0.010 mol) was mixed with acetone (50%). cm 3) and 2-ethylthio-6-aminobenzothiazole (2.10 g, 0.010 mol) with stirring at ambient temperature. The resulting dark red solution was heated to 40-45 ° C and 30% aqueous formaldehyde solution (1 cm 3, 0.010 mol) was added at this temperature. After several minutes (5 to 10) with vigorous stirring, the product of yellow color, powder consistency, crystallizes. For a further 5 minutes, the mixture was cooled to ambient temperature and the product was filtered off with suction with ethanol (20 cm 3). Yield: 3.03 g (70%).

Melting point: 183-184 ° C.

H, 4.24; N, 12.89. S, 29.51. Found: C, 47.20; H, 3.52; 11, S 29.38 Example 3

The anti-yeast activity of the composition of the invention (10 "mole dm-5) compared to that of 2-mercaptobenzothiazole (2-MBT)

Compound for example ED50 Candida albicans ED100 Saccharomyces cerevisiae ED50 ED100 1 20 87 220 850 2 26 170 320 1000 2-MBT 360 1000 520> 1000 ED 50, ED100 = concentration of the substance which inhibits the yeast propagation to 50% and 50% respectively. 100 «/ o oip opposed; > = even the concentration indicated is not sufficient.

Claims (1)

5 To determine the anti-yeast activity, a liquid synthetic formulation with vitamins (5 cm 3 in tube), static culture, temperature of 28 ° C was used. The substances dissolved in dimethylsulphoxide were fed to the post-aftercell. The proliferation of yeasts was monitored turbidimetrically and ED 50 and εΓλοο values were obtained from the constructed Example 4 growth curves. These are related to Day 6 of cultivation in Candida albicans, Day 4 of Saccharomyces cerevisiae. when controls reached maximum growth. The effectiveness of the composition according to the invention against filamentous microscopic fungi in comparison with the efficacy of 2-mercaptobenzothiazole (2-MBT). Aspergillus niger Day 4 Day 14 MIC (10 ~ e mol. Dm'3) Rhizopus oryzae Alternaria alternata Day 6 Day 14 Day 7 Day 14 1 1000 1000 200> 1000 200 1000 2> 1000> 1000 1000> 1000 1000> 1000 2-MBT> 1000> 1000> 1000>> 1000 200 1000 MIC = minimum inhibitory concentration (the lowest concentration of the test, which completely suppressed fungal growth, even the indicated concentration is not sufficient. the modified Czapek-Dox feed (20 cm 3 in Erlenmeyer flasks of 100 cm 3) with added substances dissolved in dimethylsulfoxide The resulting concentration of substances in the pool was, 1000, 200, 40 and 8 - all in (mol. dm'3) The culture was stastic, temperature 28 ° C. The growth was assessed visually, the fact that the composition of the invention is totally inhibiting the growth of Canidida albicans already at a concentration of 87.10 -6 mole dm 3 (compound according to Example 1) arast yeast Sac charomyces cerevisi-ae at a concentration of 850.1-Οΰ mole dm55 and is effective against filamentous microscopic fungi of Rhizopus oryzae and Alternaria alter-nata at a concentration of 200 .mu.-6 mol. dm'3. The composition according to the invention can be used as an active ingredient of anti-yeast preparations having a side effect against filamentous microspocic fungi, alone or in admixture with other substances. OBJECT OF THE INVENTION An anti-yeast agent composition comprising 6-nitro-3- (2-alkylthio-6-benzothiazolyl-aminomethyl) -2-benzothiazolinothione of the formula I as active ingredient wherein R is alkyl of 1 or 2 carbon atoms.