The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazon... more The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N 1-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC 50 values in the low micromolar range.
BACKGROUND:
With the ultimate goal of identifying new compounds active against root-knot nemat... more BACKGROUND:
With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita.
RESULTS:
The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC50 /24 h values of 12 ± 5 and 15 ± 4 mg L-1 respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC50 /24 h 0.4 ± 0.3 mg L-1 ). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC50 /24 h value 25 ± 17 mg L-1 ). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC50 /24 h value 26 ± 15 mg L-1 ) than 4-methoxyacetophenone (EC50 /24 h value 43 ± 10 mg L-1 ).
CONCLUSIONS:
Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients
The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazon... more The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N'-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range.
A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-... more A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-knot nematode Meloidogyne incognita. The phenylhydrazones of thiophene-2-carboxyaldehyde 5, 3-methyl-2-thiophenecarboxyaldehyde, 6, and salicylaldehyde, 2, were the most potent with EC50/48h values of 16.6 ± 2.2, 23.2 ± 2.7, and 24.3 ± 1.4 mg/L, respectively. A GC-MS metabolomics analysis, after in vitro nematode treatment with hydrazone 6 at 100 mg/L for 12 h, revealed elevated levels of fatty acids such as lauric acid, stearic acid, 2-octenoic acid, and palmitic acid. Whereas control samples showed the highest levels of monoacylglycerols such as monostearin and 2-monostearin, surprisingly, 2 h after treatment with hydrazone 6, nematodes excreted 3 times the levels of ammonia eliminated in the same conditions by controls. Thus, phenylhydrazones may represent a good scaffold in the discovery and synthesis of new nematicidal compounds, and a metabolomics approach may be helpful in understanding their mechanisms of toxicity and mode of action.
Different maleimide derivatives were synthesized and assayed for their in vitro activity on the s... more Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC 50/72h values of 2.6 ± 1.3, 5.1 ± 3.4, 16.2 ± 5.4, and 19.0 ± 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC 50 value of 48.6 ± 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at 50 mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.
The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazon... more The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N 1-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC 50 values in the low micromolar range.
BACKGROUND:
With the ultimate goal of identifying new compounds active against root-knot nemat... more BACKGROUND:
With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita.
RESULTS:
The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC50 /24 h values of 12 ± 5 and 15 ± 4 mg L-1 respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC50 /24 h 0.4 ± 0.3 mg L-1 ). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC50 /24 h value 25 ± 17 mg L-1 ). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC50 /24 h value 26 ± 15 mg L-1 ) than 4-methoxyacetophenone (EC50 /24 h value 43 ± 10 mg L-1 ).
CONCLUSIONS:
Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients
The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazon... more The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N'-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range.
A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-... more A series of aryl hydrazones were synthesized and in vitro assayed for their activity on the root-knot nematode Meloidogyne incognita. The phenylhydrazones of thiophene-2-carboxyaldehyde 5, 3-methyl-2-thiophenecarboxyaldehyde, 6, and salicylaldehyde, 2, were the most potent with EC50/48h values of 16.6 ± 2.2, 23.2 ± 2.7, and 24.3 ± 1.4 mg/L, respectively. A GC-MS metabolomics analysis, after in vitro nematode treatment with hydrazone 6 at 100 mg/L for 12 h, revealed elevated levels of fatty acids such as lauric acid, stearic acid, 2-octenoic acid, and palmitic acid. Whereas control samples showed the highest levels of monoacylglycerols such as monostearin and 2-monostearin, surprisingly, 2 h after treatment with hydrazone 6, nematodes excreted 3 times the levels of ammonia eliminated in the same conditions by controls. Thus, phenylhydrazones may represent a good scaffold in the discovery and synthesis of new nematicidal compounds, and a metabolomics approach may be helpful in understanding their mechanisms of toxicity and mode of action.
Different maleimide derivatives were synthesized and assayed for their in vitro activity on the s... more Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC 50/72h values of 2.6 ± 1.3, 5.1 ± 3.4, 16.2 ± 5.4, and 19.0 ± 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC 50 value of 48.6 ± 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at 50 mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.
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Papers by Monica Demurtas
With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita.
RESULTS:
The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC50 /24 h values of 12 ± 5 and 15 ± 4 mg L-1 respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC50 /24 h 0.4 ± 0.3 mg L-1 ). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC50 /24 h value 25 ± 17 mg L-1 ). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC50 /24 h value 26 ± 15 mg L-1 ) than 4-methoxyacetophenone (EC50 /24 h value 43 ± 10 mg L-1 ).
CONCLUSIONS:
Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients
With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita.
RESULTS:
The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC50 /24 h values of 12 ± 5 and 15 ± 4 mg L-1 respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC50 /24 h 0.4 ± 0.3 mg L-1 ). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC50 /24 h value 25 ± 17 mg L-1 ). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC50 /24 h value 26 ± 15 mg L-1 ) than 4-methoxyacetophenone (EC50 /24 h value 43 ± 10 mg L-1 ).
CONCLUSIONS:
Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients