SU1571982A1 - Derivatives of 4-carboxyvinylenchalcone having anti-fungous activity - Google Patents

Abstract

The invention relates to arbitrariness. chalcones, in particular 4-carboxy-xivinylene-4-bromo- and 4-carboxyvylene-2-hydroxy chalcones, exhibiting antifungal activity, which can be used in medicine. The goal is to create new, more active compounds of the specified class. Synthesis is carried out from sodium hydroxide, 4-formyl-cinnamic acid and 4-bromo- or 2-hydroxyacetophenone in ethanol at room temperature. Output 98.3 and 91.8%, so pl. 215-218 ° C and 157-159 ° C, the gross formula CjgHjjBrOj and C f | If M04. In comparison with griseofulvin, the antimicrobial activity of new compounds is twice as high (at the minimum effective concentration), the toxicity of LD jo 285 and 310 mg / kg versus 280 mg / kg. 1 tab. 2

Description

The invention relates to new chalcone derivatives, in particular, to 4-carboxyvinyl-4-bromo- and 4-carboxyl-soluble-2-hydroxychalcones that exhibit anti-fungal activity.

The goal is to create new biologically active compounds - chalcone derivatives with higher antifungal activity.

Example 1. 4-Carboxivinalen-4-bromochalkon 0

To a solution of 0.4 g (0.01 mol) of sodium hydroxide in 10 ml of ethanol was added 0.955 g (0.0048 mol) of para-bromoacetophenone and 0.88 g (0.0048 mol) of 4-formric acid. The reaction mixture is stirred for 1 h, then left on OA ,,,,

The reaction mixture is drunk in a mixture of ice-water acidified with hydrochloric acid. The precipitate formed is filtered and washed with water. The yield is 1.69 g (98.3%).

Crystallized from ethanol, t "pls 215-218 ° C.

Found,%: C 60,32; M 3.48; - Br 22.55.

C, vN1EKgOe.

Calculated,%: C 0.50; H 3.64, - Br 22.41.

IR spectrum data 32Г) С) -2400 (0-Н), 1715 cm- (car-carbon), 1685 cm (carbonyl.), 1615 cm-1600 cm- (), 1580 cm- (Ag), 970 cm Chtrans - OS).

UV spectrum: 2U7, 293 them.

SP h

to

GO

Example 2. 4-Carboxivipil g-2-hydroxychalcon.

To a solution of 0.6 g (0.015 mol) of sodium hydroxide in 10 ml of ethanol was added 0.65 g (0.0048 mol) of 2 psproxyacetophenone and 0.88 g (0.0048 mol) of 4-formyl-boramin acid. The reaction mixture was stirred for 1 h and left for 24 h. Then the reaction mixture is drunk into an acidified mixture with ice-water, the precipitate formed is filtered and washed with water. Output . g (9ts8%).

 Crystallized from ethanol, tg. .

1%, C: 74.32; H, 3.50. CfgH ,, 04.

Calculated,%: C 74.47- II 3.45. IR spectrum data, 3230-2400 cm-t (CHO, 1720 cm-1 (carboxyl.), 1695 (carbonyl.), 1640, if 25 cm- (OC), 1580 cm- (Ar), (9Ј0 cm - 1 (trans) „

UV spectrum, 205, 278, 350 m. Example 3. Tests for biological activity.

The determination of the antifungal activity of new compounds and reference preparations is carried out by the method of serial deputies on liquid-nutrient medium Soburo,

The following microbes are used as test microbes: Trichophyton rubrum, Trichop ™ hyiton tnentagrophytes var. interdigi-talle, Microsporum canis.

A suspension of 7-10 day cultures is used for seeding. Suspension of fungi is prepared in physiological solution according to the optical standard of turbidity at the rate of 200 thousand cells per 1 ml of nutrient medium. After additional dilutions of the standard solution, the microbial load of pathogenic fungi is 1000 fungal bodies in 1 ml of medium. Crops are inoculated in a thermostat at 2 ° C. Counting is carried out for 7-10 days. The test tubes are the nutrient medium; the seed is the same amount of test.

0

five

0

five

cultures, as well as tubes with medium and preparation, but without culture, necessary for checking turbidity and sedimentation of the preparation.

 The criterion for the fungistatic activity of the drug is the extreme concentration of the drug in a medium in which there is no visible growth of the culture at the optimum growing temperature and a given microbial load.

Determination of acute toxicity is carried out on white mice weighing 18-20 g. 0.5 ml solutions of the test substances are injected intraperitoneally. For each dose in the experiment take 6 mice.

These fungistatic activity and toxicity of chalcone derivatives and the preparation of griseofulvin are given in the table.

It follows from the table that the new compounds exhibit a high acti-fungal activity against test objects of Trichophyton mentagrophytes var. interdigitale, Microsporum canis, which is 2 times greater than the activity of the known drug griseofulvin,

4-Carboxivinylene-2-hydroxychalcone is less toxic for warm-blooded animals than the standard - the value of Y y is 310 mg / kg versus 280 mg / kg for griseofulvin.

The toxicity of 4-carboxyvinyl-4 - -bromochalcon is at the level of the reference preparation (mg / kg).

Claims (1)

Invention Formula Derivatives of 4-carboxyvinylhalkonone of the general formula I B Pi (8T p (about nn nn-soon, five 0 where RT is H; K1 - BrjVR - OH; R, - H, has antifungal activity. 51571982 Antngribkov activity of the compounds under study (in µg / ml) 4-carboxyvinyl-4-bromhalkon 3.9 4-carboxyvinylene-2-hydroxychalcon 500 Griseofulvin 3.9 Compiled by N, Kulikova Editor M. Samerkhanova Tehred M. Khodanich Proofreader M. Maksimnshinets Order 3729 R Circulation 259 VNIIPI State Committee on Inventions and Discoveries at the State Committee on Science and Technology of the USSR 113035, Moscow, Zh-35G, 4/5 Raushsk nab. Production and publishing plant. Patent, Uzhgorod, st. Gagarin, 101 3.9 ,9 285 1.9 3.9 310 280 Subscription