Characterization and Genetic Diversity of Benzimidazole-resistant and -sensitive Monilinia fructicola Isolates in Korea

Lim, Tae-Heon,Johnson, Iruthayasamy,Cha, Byeong-Jin The Korean Society of Plant Pathology 2006 Plant Pathology Journal Vol.22 No.4

To characterize benzimidazole-resistant and -sensitive Monilinia fructicola populations, the fungal isolates were obtained from peach plants showing brown rot and bloosom blight. Benzimidazole-sensitive isolates did not grow on potato dextrose agar(PDA) amended with $\geq1.0{\mu}g$ active ingredient(a.i.)/ml of the fungicides. However, benzimidazole-resistant isolates grew on PDA regardless of the tested concentrations of fungicides. Benzimidazole-resistant isolates did not grow on diethofencarb-PDA, but sensitive isolates grew on the same PDA. In the nucleotide sequences of $\beta$-tubulin gene, only codon 198(GAG: glutamic acid), a target site for benzimidazole, was replaced with GCG(alanine) in all of the resistant isolates, and this substitution seems to play an important role in the development of resistance. Other interesting codons such as 165(GCT), 200(TTC), and 241(GCT) were not changed among the isolates. Benzimidazole-resistant and -sensitive isolates were clustered clearly in random amplified polymerphic DNA analyses and the results revealed that low levels of genetic diversity between benzimidazole-sensitive and -resistant isolates of M. fructicola in the investigated regions.

Characterization and Genetic Diversity of Benzimidazole-resistant and -sensitive Monilinia fructicola Isolates in Korea

Tae Heon Lim,Iruthayasamy Johnson,차병진 한국식물병리학회 2006 Plant Pathology Journal Vol.22 No.4

To characterize benzimidazole-resistant and -sensitive Monilinia fructicola populations, the fungal isolates were obtained from peach plants showing brown rot and bloosom blight. Benzimidazole-sensitive isolates did not grow on potato dextrose agar (PDA) amended with ≥1.0 μg active ingredient (a.i.)/ml of the fungicides. However, benzimidazole-resistant isolates grew on PDA regardless of the tested concentrations of fungicides. Benzimidazole-resistant isolates did not grow on diethofencarb-PDA, but sensitive isolates grew on the same PDA. In the nucleotide sequences of β-tubulin gene, only codon 198 (GAG: glutamic acid), a target site for benzimidazole, was replaced with GCG (alanine) in all of the resistant isolates, and this substitution seems to play an important role in the development of resistance. Other interesting codons such as 165 (GCT), 200 (TTC), and 241 (GCT) were not changed among the isolates. Benzimidazole-resistant and -sensitive isolates were clustered clearly in random amplified polymerphic DNA analyses and the results revealed that low levels of genetic diversity between benzimidazole-sensitive and -resistant isolates of M. fructicola in the investigated regions.

시설재배 상추에서 Benzimidazole계 농약의 분해특성

김종필,서정미,이향희,오무술,하동룡,신현우,김은선 한국식품위생안전성학회 2008 한국식품위생안전성학회지 Vol.23 No.2

Three benzimidazole pesticides commonly used in korean lettuce were subjected to a field residue trial to ensure safety of terminal residue in the harvest. The residual patterns of three benzimidazole pesticides, which were carbendazim, benomyl and thiophanate-methyl were examined after applying with the recommended dose in two types of korean lettuce (Chima and Chuckmeon) and their DT50 were calculated. In Chima lettuce, biological half-lives of carbendazim, benomyl and thiophanate-methyl were 2.56, 1.37 and 2.54 days, respectively and their required time under MRL(5.0 mg/kg as carbendazim) were 4.5, 2.2 and 1.0days. In Chuckmeon lettuce, biological half-lives of them were 3.41, 1.70 and 4.20 days, respectively and their required time under MRL were 5.4, 1.9 and 0.5days. Three benzimidazole pesticides commonly used in korean lettuce were subjected to a field residue trial to ensure safety of terminal residue in the harvest. The residual patterns of three benzimidazole pesticides, which were carbendazim, benomyl and thiophanate-methyl were examined after applying with the recommended dose in two types of korean lettuce (Chima and Chuckmeon) and their DT50 were calculated. In Chima lettuce, biological half-lives of carbendazim, benomyl and thiophanate-methyl were 2.56, 1.37 and 2.54 days, respectively and their required time under MRL(5.0 mg/kg as carbendazim) were 4.5, 2.2 and 1.0days. In Chuckmeon lettuce, biological half-lives of them were 3.41, 1.70 and 4.20 days, respectively and their required time under MRL were 5.4, 1.9 and 0.5days.

Synthesis and in vitro Antitumor Activity of 2-Alkyl, 2-Aryl, and 2-Piperazinyl Benzimidazole-4, 7-dione Derivatives

Ahn, Chan-Mug,Tak, Jung-Ae,Choi, Sun-Ju The Pharmaceutical Society of Korea 2000 Archives of Pharmacal Research Vol.23 No.4

A series of 2-alkyl, 2-aryl, and 2-piperazinyl benzimidazole-4,7-dione derivatives (7a-h) and 16m-o) were prepared, and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia cell line P388, and human gastric carcinoma cell lines SNU-1 and SNU-16). These compounds showed potent cytotoxicity against all of three cell lines tested, and especially SNU-16 was sensitive to them. 2-Aryl (7g,h) and 2-piperazinyl benzimidazole-4,7-dione derivative (I6 m) were more potent than mitomycin C against P388 and SNU-16. Among benzimidazole-4,7-dione derivatives with alkyl group at position 2, 7a had the most potent cytotoxicity against all of the cell lines tested.

Synthesis of 6-Aziridinylbenzimidazole Derivatives and Their In Vitro Antitumor Activities

Ahn, Chan-Mug,Kim, Soo-Kie,Han, Jeong-Lim The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.5

In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were wuperior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested.

Synthesis, Pharmacological Activity Evaluation and Molecular Modeling of New Polynuclear Heterocyclic Compounds Containing Benzimidazole Derivatives

Fatma A. Bassyouni,Tamer S. Saleh,Mahmoud M. ElHefnawi,Sherein I. Abd El-Moez,Waled M. El-Senousy,Mohamed E. Abdel-Rehim 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.12

Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1Hbenzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4'',5''-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophorebased correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation.

Analyses of the Less Benzimidazole-sensitivity of the Isolates of Colletotrichumspp. Causing the Anthracnose in Pepper and Strawberry

Yun-Sik Kim,Ji Young Min,Beum Kwan Kang,Ngyeun Van Bach,Woo Bong Choi,박은우,김흥태 한국식물병리학회 2007 Plant Pathology Journal Vol.23 No.3

The anthracnose disease on pepper fruits in Korea was caused by Colletotrichum acutatum as well as C. gloeosporioides. Since C. acutatum showed less sensitivity to benomyl, it was analyzed whether the less sensitivity was given by the same mechanism for the fungicide resistance of C. gloeosporioides. The isolates of C. acutatum were less sensitive to the three benzimidazole fungicides tested, benomyl, carbendazim, and thiophanate- methyl. However, the of C. acutatum isolates were different from the resistant isolates of C. gloeosporioides in their response to diethofencarb, one of N-phenylcarbamates; the former was still less sensitive to diethofencarb than the latter. The differences in the resistance mechanisms in two species were conspicuous in sequence analysis of the tub2 genes. The genes from C. acutatum did not show any non-synonymous base substitutions at the regions known to be correlated with the benzimidazole-resistance. All of these data may indicate that the less sensitivity of C. acutatum to benomyl is based on different mechanism(s) from that of C. gloeosporioides.

Analyses of the Less Benzimidazole-sensitivity of the Isolates of Colletotrichum spp. Causing the Anthracnose in Pepper and Strawberry

Kim, Yun-Sik,Min, Ji-Young,Kang, Beum-Kwan,Bach, Ngyeun-Van,Choi, Woo-Bong,Park, Eun-Woo,Kim, Heung-Tae The Korean Society of Plant Pathology 2007 Plant Pathology Journal Vol.23 No.3

The anthracnose disease on pepper fruits in Korea was caused by Colletotrichum acutatum as well as C. gloeosporioides. Since C. acutatum showed less sensitivity to benomyl, it was analyzed whether the less sensitivity was given by the same mechanism for the fungicide resistance of C. gloeosporioides. The isolates of C. acutatum were less sensitive to the three benzimidazole fungicides tested, benomyl, carbendazim, and thiophanate-methyl. However, the of C. acutatum isolates were different from the resistant isolates of C. gloeosporioides in their response to diethofencarb, one of N-phenyl-carbamates; the former was still less sensitive to diethofencarb than the latter. The differences in the resistance mechanisms in two species were conspicuous in sequence analysis of the tub2 genes. The genes from C. acutatum did not show any non-synonymous base substitutions at the regions known to be correlated with the benzimidazole-resistance. All of these data may indicate that the less sensitivity of C. acutatum to benomyl is based on different mechanism(s) from that of C. gloeosporioides.

Synthesis, Photophysical and Electrochemical Properties of Novel Conjugated Donor-Acceptor Molecules Based on Phenothiazine and Benzimidazole

Xiao-Hang Zhang,Seon Ho Kim,In Su Lee,Chun Ji Gao,Sung Ik Yang*,Kwang-Hyun Ahn* 대한화학회 2007 Bulletin of the Korean Chemical Society Vol.28 No.8

Two series of new organic fluorophores such as asymmetrical 3-(benzimidazol-2-yl)-10-hexylphenothiazine derivatives 1 and symmetrical 3,7-bis(benzimidazol-2-yl)-10-hexylphenothiazine derivatives 2 have been synthesized. Electronic absorption, fluorescence, and electrochemistry measurements reveal that the electron withdrawing benzimidazole subunit directly connected to the phenothiazine core facilitates the charge transfer characters which were also verified by the theoretical calculations. Various substituents on the benzimidazole moieties can allow a fine-tuning of the LUMO energy levels of the molecules without significantly affecting the HOMO energy levels. The method provides a new route for designing ambipolar molecules whose energy levels are well-matched with the Fermi levels of the electrodes to facilitate the electron or hole injection/transfer in OLED devices.

Synthesis, Photophysical and Electrochemical Properties of Novel Conjugated Donor-Acceptor Molecules Based on Phenothiazine and Benzimidazole

Zhang, Xiao-Hang,Kim, Seon-Ho,Lee, In-Su,Gao, Chun-Ji,Yang, Sung-Ik,Ahn, Kwang-Hyun Korean Chemical Society 2007 Bulletin of the Korean Chemical Society Vol.28 No.8

Two series of new organic fluorophores such as asymmetrical 3-(benzimidazol-2-yl)-10-hexylphenothiazine derivatives 1 and symmetrical 3,7-bis(benzimidazol-2-yl)-10-hexylphenothiazine derivatives 2 have been synthesized. Electronic absorption, fluorescence, and electrochemistry measurements reveal that the electron withdrawing benzimidazole subunit directly connected to the phenothiazine core facilitates the charge transfer characters which were also verified by the theoretical calculations. Various substituents on the benzimidazole moieties can allow a fine-tuning of the LUMO energy levels of the molecules without significantly affecting the HOMO energy levels. The method provides a new route for designing ambipolar molecules whose energy levels are well-matched with the Fermi levels of the electrodes to facilitate the electron or hole injection/transfer in OLED devices.