A New Piperazinobiguanide Series Effective Against Syphacia Obvelata in Mice

A

NEW

PIPERAZINOBIGUANIDE

AGAINST

SERIES

SYPHACIA

OBVELATA

EFFECTIVE IN

MICE

K.C. SINGHAL Department of Pharniwology,

J.N. Medical College, Aligarh, India

Acccpted February

Brown derivatives

et al (1) and Harfenist against

study by screening by Chan

Syphacia

et al (2) have evaluated

obeeelata in mice.

more of these derivatives.

(3) was used to obtain

relatively

water

together

500 mg/kg

weight.

with gum acacia

on the day of treatment day following

body

It was thought

uniform

Each

infection Drugs

the treatment.

and administered

Contents

worthwhile exposure in mice.

orally.

of caecum

of piperazine to extend

method

in 0.5 ml of distilled

Autopsy

and rectum

mice

in doses of

The mice were allowed was carried

were brushed

water and worm count was done against

this

described

The infected

were administered

dose was suspended

and were fasted again the next day.

into a petri dish containing

a large number

The laboratory

were fasted for one day prior to drug treatment. 100, 200 and

21, 1975

food on the

out gently

a black background.

SHORT

COMMUNICATIONS

Japan. J. Pharmacol. 25, 353 (1975)

TABLE1.

The dose response was estimated according to the proportion of mice cleared of infection and compared with piperazine citrate which served as the standard.

The approximate

LD50 of active compounds was determined on albino mice weighing between 20-25 G. Table I summarizes the results. at 200 mg/kg dose.

PPb (N-phenyl) cleared all the mice of S. obvelata

The lower dose of 100 mg/kg did not show any effect.

PPb (N-ac'

pip), in which phenyl ring is substituted for the acetyl group, was found ineffective up to a dose of 500 mg/kg. PPb (N-0-tolyl), with methyl group at ortho position, exhibited a dose dependent response. kg.

It cleared 82.5 % of the mice of their infection at a dose of 100 mg/

This effect was equal to that observed with 200 mg/kg of piperazine citrate.

PPb

(N-p-tolyl) in which the methyl group is substituted in the para position cleared 100% mice of their infection at 500 mg/kg dose. The lower dose of 200 mg/kg was found to be in effective. None of the seven quinazolone derivatives tested for anthelmintic

activity against

S. ohvelata, was found to be active up to a dose of 500 mg/kg orally (Table 1). The presence of a phenyl substitution in the biguanide derivative of piperazine ap pears essential for anthelmintic activity.

This is evident from the observation that its

SHORT replacement

COMMUNICATIONS

by the acetyl group

sent findings are not in parallel

results

Japan. J. Pharmacol. 25, 354 (1975)

in abolition

with the conclusions

of the activity,

base and its simple salts are more effective against S. obrelata stituted position vity.

compounds. enhances However,

Further, the activity,

substitution

of a methyl group

while substitution

1).

The pre

than are more complex

activity

as is evident from the column

sub

in the phenyl ring at ortho

at the para position,

with the increase in the anthelmintic

toxicity of the compounds

(Table

of Brown et al (1) that the piperazine

decreases

the acti

there is also an increase in

3 of Table 1.

REFERENCES 1) BROWN,H.W., CHAN, K.F. AND 1-IussAY,K.L.: Ain. J. Trop. Med. Hvg., 3, 504-510, 1954; 2) HARFENIST,M., FANELLI,R.V., BALTZLY,R., BROWN,H.W., HUSSAY,K.L. AND CHAN, K.F.: J. Pharmacol. exp. Ther., 121, 347-353, 1957; 3) CHAN, K.F.: Am. J. Hyg., 56, 22-30, 1952