Synthesis and biological activity of certain derivatives of anesthesine (Benzocaine)

Article abstract of DOI:10.1134/S1070363208060261

Certain derivatives of ethyl p-aminobenzoate were synthesized with the purpose of creating biologically active oligomeric condensation products.

Full text of DOI:10.1134/S1070363208060261

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 6, pp. 1253–1254. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.Kh. Zhakina, M.Yu. Kurapova, A.M. Gazaliev, O.A. Nurkenov, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 6,
pp. 1026–1027.
Synthesis and Biological Activity of Certain Derivatives
of Anesthesine (Benzocaine)
A. Kh. Zhakina, M. Yu. Kurapova, A. M. Gazaliev, and O. A. Nurkenov
Institute of Organic Synthesis and Coal Chemistry of the Kazakhstan Republic,
ul. Alikhanova 1, Karaganda, 100000 Kazakhstan
e-mail: kurapova83@mail.ru
Received November 2, 2007
Abstract—Certain derivatives of ethyl p-aminobenzoate were synthesized with the purpose of creating
biologically active oligomeric condensation products.
DOI: 10.1134/S1070363208060261
Currently revealing substances
possessing
The cytotoxicity of ethyl 4-amino-3-(cytisino-
methyl)benzoate was estimated in the test of survival
rate of Artemia salina (Leach) sea crayfish maggots
by the Brine shrimp cytotoxicity method [1–5].
bactericidal activity toward the microorganism strains
playing a role in human pathology is of great
importance. The demand for new antimicrobial and
antitumor agents is also growing.
The antimicrobial activity of ethyl 4-amino-3-
(cytisinomethyl)benzoate was tested using test strains
recommended by the State Pharmacopoeia: Staphylo-
coccus aureus ATSS 6538, Bacillus subtilis ATSS
6633, Escherichia coli ATSS 25922, Pseudomonas
Continuing search for biologically active compounds
among p-aminobenzoic acid derivatives, we reacted ethyl
4-aminobenzoate and a 40% solution of formaldehyde
in boiling water at pH 1–2 under atmospheric pressure and
then modified the preparated novolak with secondary aeruginosa ATSS 9027, and Candida albicans yeast
amines (piperidine, morpholine, anabasine, and cytisine):
fungus ATSS 885-653.
To find out whether the prepared compounds are
feasible for treating germ diseases, we tested ethyl 4-
amino-3-(cytisinomethyl)benzoate (IV) for antimic-
robial and cytotoxic activity (Tables 1 and 2).
It was established that compound IV shows an
expressed antifungal activity Candida albicans yeast
fungus and an expressed cytotoxic activity toward
Artemia salina sea crayfish maggots.
CH2Cl
H+
C2H5OOC
NH2 + CH2O
C2H5OOC
C2H5OOC
NH2
_H2O
CH2Cl
NH2 + HN
CH2N
NH2
C2H5OOC
HN
_HCl
NH
;
;
O
;
HN
N
H
N
O
I
II
III
IV
1253

1254
ZHAKINA et al.
Table 1. Cytotoxicity testing resultsa
Maggots death rate after 24 h
LD50,
μg ml–1
95% confidence
interval
Compound
Activity
100 μg ml–1
10 μg ml–1
1 μg ml–1
Ethyl 4-amino-3-(cytisinomethyl) benzoate
89.91
46.62
26.64
6.895
2.894–14.601
Possesses
a
Growth inhibition zone is absent. The growth inhibition zone diameters (GIZD) smaller than 10 mm and continuous growth in a cup were
assessed as absence of antibacterial activity, GIZD 10–15 mm, as weak activity, GIZD 15–20 mm, as moderate activity, and GIZD > 20 mm,
as expressed activity.
Table 2. Antimicrobial activity testing results
Staphylococcus
aureus
Bacillus
subtilis
Escherichia
coli
Pseudomonas
aeruginosa
Candida
Сщьзщгтв
аlbicans
Ethyl 4-amino-3-(cytisinomethyl)
benzoate
Lincomycin hydrochloride
16 0.1
24 0.1
17 0.1
22 0.1
18 0.2
21 0.2
16 0.2
21 0.2
–
22 0.1
Nystatine
EXPERIMENTAL
Ethyl 4-amino-3-(cytisinomethyl)benzoate (IV)
was prepared in a similar way. Yield 45%, mp 168–
169ºC.
Ethyl [4-amino-3-(piperidinomethyl)]benzoate (I).
Concentrated hydrochloric acid, 0.5 ml, 40% formal-
dehyde, and 2.12 g of piperidine were added to 4.1 g of
aqueous anesthesine. The mixture was heated on a
boiling water bath for 3 h, and water was then distilled
off at the same temperature in water-jet-pump vacuum.
The product was purified and recrystallized from
alcohol. Yield 73 %, mp 132–133°C.
REFERENCES
1. Meyer, B.N. Ferrigni, N.R. Putnam, J.E. Jacobsen, L.B.
Nichols, D.E., and McLaughlin, J.L., Planta Medica,
1982, vol. 45, p. 31.
2. Ferrigni, N.R. and McLaughlin, J.L, J. Natural Products,
1984, vol. 47, no.2, p. 347.
Ethyl 4-amino-3-(morpholinomethyl)benzoate (II)
was prepared in a similar way. Yield 54%, mp 157–
158ºC.
3. McLaughlin, J.L., Methods Plant Bichem., 1991, vol. 6,
p. 1.
4. Beloz, A., J. Ethnopharmacol., 1992, vol. 37, p. 225.
Ethyl 4-amino-3-(anabasinomethyl)benzoate (III)
was prepared in a similar way. Yield 51%, mp 137–
138ºC.
5. Taha, A. and Alsayed, H., Phytother. Res., 2000, vol. 14,
p. 48.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 6 2008