G. Turan-Zitouni et al. / Il Farmaco 57 (2002) 573–575
575
3.2. Biological assays
4. Results and discussion
The reaction of 2-chloro-N-(5-substituted-2,3-dihy-
dro-3-benzofuryl)acetamides (1) with 3-(aryloxyalkyl)-4-
ethyl/phenyl-5-mercapto-1,2,4-triazoles (2), resulted in
3-[5-(substitutedphenoxalkyl)-4-ethyl/phenyl-1,2,4-tri-
azole-3-yl)thioacetylamino]-5-substituted-2,3-dihydro-
benzofurane (3a–q). The structure of those compounds
All compounds were submitted to a general prelimi-
nary screening including the laboratory tests for algae,
lemna, cell suspension, shoot and screening (in the
greenhouse trials) for herbicidal activity.
3.2.1. Algae test
1
was confirmed by IR, H NMR and mass spectral data.
The algae test is carried out with Scenedesmus acutus
in an autotroph Shakeculture, kept at 22 °C and under
continuous light. Algae growth is determined quantita-
tively by means of a Coulter Counter for 24 h after
compound application. The initial compound concentra-
tion is 10−4 M. If, the growth inhibition is greater than
50%, further tests at lower compound concentrations
(10−5–10−6 M.) are to be performed.
IR data were very informative. The amid carbonyl
bonds which are common in all compounds are observed
at about 1670–1645 cm−1. In the NMR spectra HA, HM
and HX protons of 2,3-dihydro-benzofuran resonate
according to the AMX system. These protons obtained
at about 4.2–4.3 ppm as quartet, 4.5–4.7 ppm as triplet
and 5.4–5.6 ppm as multiplet, respectively.
All compounds were inactive for herbicidal activity.
3.2.2. Cell suspension test
References
Two milliliter samples of cell suspension cultures are
placed in sterile test tubes. Defined quantities of the
compounds are dissolved in acetone and added to the
suspensions. After an incubation period of 8 days the
conductivity of the culture medium is determined as a
growth parameter. The effect of a compound is ex-
pressed as growth inhibition in percent with reference to
the control, with zero (0) indicating no growth inhibition
and 100, the total growth inhibition.
[1] F. Chaillet, E. Phillippot, M.G. Dallemagne, Benzofurans, XX.
Adrenergic and cholinergic properties of 5-(N-piperidi-
nomethyl)coumarylamide, Arch. Int. Pharmacodyn. 164 (1966)
466–469.
[2] R. Fielden, A.M. Roe, G.L. Willey, The adrenergic-neron blocking
action of some coumaran compounds, Br. J. Pharmacol. 23 (1964)
486–507.
[3] G. Turan-Zitouni, G. Berge, A.M. Noel-Artis, P. Chevallet, P.
Fulcrand, J. Castel, Q.S.A.R. de de´rive´s de dihydro-2,3 benzo-
furannamine-3 inhibiteurs de croissance ve´ge´tale, Farmaco Ed. Sci.
43 (1988) 643–648.
8
[4] G. Turan-Zitouni, S¸. Demirayak, K. Erol, M. Ozdemir, Synthe`se
3.2.3. Lemna test
de certains de´rive´s de methoxy-5[(benzazole-2-yl) thioacety-
lamino]-3 dihydro-2,3 benzofurane et recherche´d activite´ antihy-
pertensive, Boll. Chim. Farmaceutico 133 (1994) 148–151.
[5] G. Turan-Zitouni, Z.A. Kaplancikli, Synthesis and analgesic
activity of some triazoles and triazolothiadiazines, Farmaco 52
(1997) 635–670.
The lemna test is carried out with Lemna paucicostata.
The plants are cultured under sterile, autotrophic condi-
tions and continuous light.
The test compounds are added with the inorganic
nutrients at an initial concentration of 10−4 M. Eight
days after application the lemna growth is determined
with an image analysing apparatus. (When growth inhi-
bition is greater than 50% further tests at lower com-
pounds concentrations are generally performed.)
[6] B.S. Holla, K.A. Poojary, B. Kalluray, Synthesis characterization
and antifungal activity of some N-bridge heterocyles derived from
3-(3-bromo-4-methoxyphenyl)-4-amino-5-mercapto-1,2,4-tria-
zole, Farmaco 51 (1996) 793–799.
[7] A.R. Prasad, A.N. Rao, T. Ramalingam, P.B. Sattur, Fused
triazoles: synthesis and antifungal activity of 2-arylidene-thiazolo
[3%,2%:1,2]imidazo[5,4-b]pyridin-3(2H)-ones, 2-arylidene-thiazolo-
[3,2-a]benzimidazol-3(2H)-ones and 6-arylidene-thiazolo[3,2-b]-s-
triazol-5(6H)-ones, Indian J. Chem. Sect. B 25 (1986) 776–778.
[8] B.S. Holla, M.K. Shivanda, P.M. Akberali, S. Baliga, S. Safeer,
Studies on arylfuran derivatives. Part VI. Synthesis, characteriza-
tion and antibacterial activities of some 6-(5-aryl-2-furyl)-1,2,4-tri-
azolo[3,4-b]-1,3,4-thiadiazoles and 6-(5-nitro-5-furyl)-1,2,4-tria-
zolo[3,4-b]-1,3,4-thiadiazoles, Farmaco 51 (1996) 785–792.
[9] G. Turan-Zitouni, Z.A. Kaplancikli, Some new 2,3-dihydro-3
benzofuranamine derivatives, Bollettino Chimico Farmaceutico
137 (1998) 364–367.
[10] A.K. Sen-Gupta, O.P. Bajaj, U. Chandra, Synthesis and antibac-
terial activity of some phenoxyacetyl thiosemicarbazides, substi-
tuted 1,3,4-oxadiazoles, 1,2,4-triazoles and alkyl/phenyl
carbamates of substituted 1,3,4-oxadiazole-2-thiones, J. Indian
Chem. Soc. 55 (1978) 962–964.
[11] S.P. Suman, S.C. Bahel, Some fungicidal 3-aryl/aryloxymethyl-4-
aryl-5-mercapto-1,2,4-triazoles and bis(3-aryloxymethyl-4-aryl-
1,2,4-triazol-5-yl)methylene/ethylene disulfides, J. Indian Chem.
Soc. 57 (1980) 420–422.
3.2.4. Shoot test with Sinapis alba
Two leaf stage shoots, detached from mustard
seedlings, are placed upright in plastic vials each of
which initially containing 10−4 M of the test compound
in distilled water. After 3 days, changes in the shoot fresh
weight are determined.
3.2.5. Screening for herbicidal acti6ity
A suitable spectrum of mono- and dicotyledonous
plants is reared in the greenhouse and treated with the
compounds, either pre-emergence or post-emergence.
The normal application rate is equivalent to 3 kg/ha.
The damage caused to the test plants is recorded as a
percentage, where 0 represents no damage and 100, total
damage.
Turan-Zitouni
