In vitro screening of 1-aryl-6-hydroxy-1,2,3,4-tetrahydroisoquinolines: structure related activity against pathogenic bacteria
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摘要
Objective: To evaluate the antibacterial activity of ten synthetic tetrahydroisoquinolines against eight bacterial strains. Methods: The ten tetrahydroisoquinolines synthesized via base-catalyzed Pictet-Spengler cyclization were screened against a total of eight bacterial strains comprising control and pathogenic strains by the disc diffusion and micro-dilution methods. The most active compound was then assessed for cytotoxicity on human lymphocytes. Results: Six of the tetrahydroisoquinolines showed broad spectrum bacteriostatic activity. The zones of inhibition produced ranged from 7 to 23 mm for 200 μg per disc. The presence of a lipophilic substituent at the para position of the pendant phenyl group conferred the highest antibacterial activity. Compound 2 [1-(3,4-chlorophenyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline] was the most active and produced zones ranging from 9 to 20 mm against all eight bacterial strains. Compound 2 also showed the lowest minimum inhibitory concentration of 100 μg/mL against Escherichia coli ATCC11775 and the lowest minimum bactericidal concentration of 800 μg/mL against pathogenic Salmonella typhimurium. Overall, compound 2 was the most active with bacteriostatic and bactericidal activity against three and four bacterial strains respectively. A 50% cytotoxic concentration of 98.2 μg/mL was recorded for compound 2 indicating a low risk of toxicity. Conclusions: The 1-aryl-1,2,3,4-tetrahydroisoquinolines display structure-related antibacterial activity and further chemical exploration of the tetrahydroisoquinoline scaf old may yield more potent non-toxic derivatives for development into new antibacterials.
Objective: To evaluate the antibacterial activity of ten synthetic tetrahydroisoquinolines against eight bacterial strains. Methods: The ten tetrahydroisoquinolines synthesized via base-catalyzed Pictet-Spengler cyclization were screened against a total of eight bacterial strains comprising control and pathogenic strains by the disc diffusion and micro-dilution methods. The most active compound was then assessed for cytotoxicity on human lymphocytes. Results: Six of the tetrahydroisoquinolines showed broad spectrum bacteriostatic activity. The zones of inhibition produced ranged from 7 to 23 mm for 200 μg per disc. The presence of a lipophilic substituent at the para position of the pendant phenyl group conferred the highest antibacterial activity. Compound 2 [1-(3,4-chlorophenyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline] was the most active and produced zones ranging from 9 to 20 mm against all eight bacterial strains. Compound 2 also showed the lowest minimum inhibitory concentration of 100 μg/mL against Escherichia coli ATCC11775 and the lowest minimum bactericidal concentration of 800 μg/mL against pathogenic Salmonella typhimurium. Overall, compound 2 was the most active with bacteriostatic and bactericidal activity against three and four bacterial strains respectively. A 50% cytotoxic concentration of 98.2 μg/mL was recorded for compound 2 indicating a low risk of toxicity. Conclusions: The 1-aryl-1,2,3,4-tetrahydroisoquinolines display structure-related antibacterial activity and further chemical exploration of the tetrahydroisoquinoline scaf old may yield more potent non-toxic derivatives for development into new antibacterials.
Objective: To evaluate the antibacterial activity of ten synthetic tetrahydroisoquinolines against eight bacterial strains. Methods: The ten tetrahydroisoquinolines synthesized via base-catalyzed Pictet-Spengler cyclization were screened against a total of eight bacterial strains comprising control and pathogenic strains by the disc diffusion and micro-dilution methods. The most active compound was then assessed for cytotoxicity on human lymphocytes. Results: Six of the tetrahydroisoquinolines showed broad spectrum bacteriostatic activity. The zones of inhibition produced ranged from 7 to 23 mm for 200 μg per disc. The presence of a lipophilic substituent at the para position of the pendant phenyl group conferred the highest antibacterial activity. Compound 2 [1-(3,4-chlorophenyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline] was the most active and produced zones ranging from 9 to 20 mm against all eight bacterial strains. Compound 2 also showed the lowest minimum inhibitory concentration of 100 μg/mL against Escherichia coli ATCC11775 and the lowest minimum bactericidal concentration of 800 μg/mL against pathogenic Salmonella typhimurium. Overall, compound 2 was the most active with bacteriostatic and bactericidal activity against three and four bacterial strains respectively. A 50% cytotoxic concentration of 98.2 μg/mL was recorded for compound 2 indicating a low risk of toxicity. Conclusions: The 1-aryl-1,2,3,4-tetrahydroisoquinolines display structure-related antibacterial activity and further chemical exploration of the tetrahydroisoquinoline scaf old may yield more potent non-toxic derivatives for development into new antibacterials.
引文
[1]World Health Organization.Fact sheet No 310:the top ten causes of death.Geneva:World Health Organization;2014.[Online]Available from:http://www.who.int/mediacentre/factsheets/fs310/en/[Accessed on 20th October,2014]
[2]Davies J,Davies D.Origins and evolution of antibiotic resistance.Microbiol Mol Biol Rev 2010;74:417-33.
[3]Bassetti M,Merelli M,Temperoni C,Astilean A.New antibiotics for bad bugs:where are we?Ann Clin Microbiol Antimicrob 2013;12:22.
[4]Lewis K.Platforms for antibiotic discovery.Nat Rev Drug Discov 2013;12:371-87.
[5]Mshana SE,Matee M,Rweyemamu M.Antimicrobial resistance in human and animal pathogens in Zambia,Democratic Republic of Congo,Mozambique and Tanzania:an urgent need of a sustainable surveillance system.Ann Clin Microbiol Antimicrob 2013;12:28.
[6]Hoffmann K,Wagner G,Apfalter P,Maier M.Antibiotic resistance in primary care in Austria–a systematic review of scientific and grey literature.BMC Infect Dis 2011;11:330.
[7]Ndip RN,Ntiege EA,Ndip LM,Nkwelang G,Akoachere JF,Akenji TN.Antimicrobial resistance of bacterial agents of the upper respiratory tract of school children in Buea,Cameroon.J Health Popul Nutr 2008;26(4):397-404.
[8]Silver LL.Challenges of antibacterial discovery.Clin Microbiol Rev 2011;24(1):71-109.
[9]Ngo HJ,Ntie-Kang F,Kaiser M,Brun R,Efange SMN.1-Aryl-1,2,3,4 tetrahydroisoquinolines as potential antimalarials:synthesis,in vitro antiplasmodial activity and in silico pharmacokinetics evaluation.RSC Adv2014;4:22856-65.
[10]Murahashi SI,Shiola T.Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide.Simple synthesis of nitrones from secondary amines.Tetrahedron Lett 1987;28(21):2383-6.
[11]Bringmann G,Brun R,Kaiser M,Neumann S.Synthesis and antiprotozoal activity of simplified analogs of naphthylisoquinoline alkaloids.Eur J Med Chem 2008;43(1):32-42.
[12]Liu ZZ,Tang YF,Chen SZ.Formation of benzyl oxazole,a competitive path with the classical Bishler-Napieralski reaction.Chin Chem Lett 2001;12:947-50.
[13]Bringmann G,Feineis D,God R,Peters K,Peters EM,Scholz J,et al.1-Trichloromethyl–1,2,3,4-tetrahydrobetacarboline(Ta Clo)and related derivates:chemistry and biochemical effects on catecholamine biosynthesis.Bioorg Med Chem 2002;10:2207-14.
[14]Scott JD,Williams RM.Total Synthesis of(-)-tetrazomine and Determination of its stereochemistry.Angew Chem Int Ed 2001;40(8):1463-5.
[15]Mbah JA,Ngemenya MN,Abawah AL,Babiaka SB,Nubed LN,Nyongbela KD,et al.Bioassay-guided discovery of antibacterial agents:in vitro screening of Peperomia vulcanica,Peperomia fernandopoioana and Scleria striatinux.Ann Clin Microbiol Antimicrob 2012;11:10.
[16]Lehtopolku M,Kotilainen P,Puukka P,Nakari UM,Siitonen A,Eerola E,et al.Inaccuracy of the disk diffusion method compared with the agar dilution method for susceptibility testing of Campylobacter spp.J Clin Microbiol2012;50(1):52-6.
[17]Zofou D,Tene M,Ngemenya MN,Tane P,Titanji VP.I n vitro antiplasmodial activity and cytotoxicity of extracts of selected medicinal plants used by traditional healers of Western Cameroon.Malar Res Treat2011;doi:10.4061/2011/561342.
[18]Li G,Wang X,Huang LH,Wang Y,Hao JJ,Ge X,et al.Cytotoxic function of CD8+T lymphocytes isolated from patients with acute severe cerebral infarction:an assessment of stroke-induced immunosuppression.BMC Immunol 2013;14:1.
[19]Bueno DC,Meinerz DF,Allebrandt J,Waczuk EP,Bonfanti dos Santos D,Mariano DOC,et al.Cytotoxicity and genotoxicity evaluation of organochalcogens in human leucocytes:a comparative study between ebselen,diphenyl diselenide,and diphenyl ditelluride.Bio Med Res Int2013;doi:10.1155/2013/537279.
[20]Clinical and Laboratory Standards Institute:Performance standards for antimicrobial susceptibility testing;twenty second informational supplement M100–S22.Wayne;Clinical and Laboratory Standards Institute;2012.[Online]Available from:http://antimicrobianos.com.ar/ATB/wp-content/uploads/2012/11/M100S22E.pdf[Accessed on 20th October,2014]
[21]Malebo HM,Tanja W,Cal M,Swaleh SAM,Omolo MO,Hassanali A,et al.Antiplasmodial,antitrypanosomal,antileshmanial and cytotoxicity activity of selected Tanzanian medicinal plants.Tanzan J Health Res 2009;11(4):226-34.
[22]Tiwari RK,Singh D,Singh J,Chhillar AK,Chandra R,Verma AK.Synthesis,antibacterial activity and QSAR studies of 1,2-disubstituted-
[2]Davies J,Davies D.Origins and evolution of antibiotic resistance.Microbiol Mol Biol Rev 2010;74:417-33.
[3]Bassetti M,Merelli M,Temperoni C,Astilean A.New antibiotics for bad bugs:where are we?Ann Clin Microbiol Antimicrob 2013;12:22.
[4]Lewis K.Platforms for antibiotic discovery.Nat Rev Drug Discov 2013;12:371-87.
[5]Mshana SE,Matee M,Rweyemamu M.Antimicrobial resistance in human and animal pathogens in Zambia,Democratic Republic of Congo,Mozambique and Tanzania:an urgent need of a sustainable surveillance system.Ann Clin Microbiol Antimicrob 2013;12:28.
[6]Hoffmann K,Wagner G,Apfalter P,Maier M.Antibiotic resistance in primary care in Austria–a systematic review of scientific and grey literature.BMC Infect Dis 2011;11:330.
[7]Ndip RN,Ntiege EA,Ndip LM,Nkwelang G,Akoachere JF,Akenji TN.Antimicrobial resistance of bacterial agents of the upper respiratory tract of school children in Buea,Cameroon.J Health Popul Nutr 2008;26(4):397-404.
[8]Silver LL.Challenges of antibacterial discovery.Clin Microbiol Rev 2011;24(1):71-109.
[9]Ngo HJ,Ntie-Kang F,Kaiser M,Brun R,Efange SMN.1-Aryl-1,2,3,4 tetrahydroisoquinolines as potential antimalarials:synthesis,in vitro antiplasmodial activity and in silico pharmacokinetics evaluation.RSC Adv2014;4:22856-65.
[10]Murahashi SI,Shiola T.Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide.Simple synthesis of nitrones from secondary amines.Tetrahedron Lett 1987;28(21):2383-6.
[11]Bringmann G,Brun R,Kaiser M,Neumann S.Synthesis and antiprotozoal activity of simplified analogs of naphthylisoquinoline alkaloids.Eur J Med Chem 2008;43(1):32-42.
[12]Liu ZZ,Tang YF,Chen SZ.Formation of benzyl oxazole,a competitive path with the classical Bishler-Napieralski reaction.Chin Chem Lett 2001;12:947-50.
[13]Bringmann G,Feineis D,God R,Peters K,Peters EM,Scholz J,et al.1-Trichloromethyl–1,2,3,4-tetrahydrobetacarboline(Ta Clo)and related derivates:chemistry and biochemical effects on catecholamine biosynthesis.Bioorg Med Chem 2002;10:2207-14.
[14]Scott JD,Williams RM.Total Synthesis of(-)-tetrazomine and Determination of its stereochemistry.Angew Chem Int Ed 2001;40(8):1463-5.
[15]Mbah JA,Ngemenya MN,Abawah AL,Babiaka SB,Nubed LN,Nyongbela KD,et al.Bioassay-guided discovery of antibacterial agents:in vitro screening of Peperomia vulcanica,Peperomia fernandopoioana and Scleria striatinux.Ann Clin Microbiol Antimicrob 2012;11:10.
[16]Lehtopolku M,Kotilainen P,Puukka P,Nakari UM,Siitonen A,Eerola E,et al.Inaccuracy of the disk diffusion method compared with the agar dilution method for susceptibility testing of Campylobacter spp.J Clin Microbiol2012;50(1):52-6.
[17]Zofou D,Tene M,Ngemenya MN,Tane P,Titanji VP.I n vitro antiplasmodial activity and cytotoxicity of extracts of selected medicinal plants used by traditional healers of Western Cameroon.Malar Res Treat2011;doi:10.4061/2011/561342.
[18]Li G,Wang X,Huang LH,Wang Y,Hao JJ,Ge X,et al.Cytotoxic function of CD8+T lymphocytes isolated from patients with acute severe cerebral infarction:an assessment of stroke-induced immunosuppression.BMC Immunol 2013;14:1.
[19]Bueno DC,Meinerz DF,Allebrandt J,Waczuk EP,Bonfanti dos Santos D,Mariano DOC,et al.Cytotoxicity and genotoxicity evaluation of organochalcogens in human leucocytes:a comparative study between ebselen,diphenyl diselenide,and diphenyl ditelluride.Bio Med Res Int2013;doi:10.1155/2013/537279.
[20]Clinical and Laboratory Standards Institute:Performance standards for antimicrobial susceptibility testing;twenty second informational supplement M100–S22.Wayne;Clinical and Laboratory Standards Institute;2012.[Online]Available from:http://antimicrobianos.com.ar/ATB/wp-content/uploads/2012/11/M100S22E.pdf[Accessed on 20th October,2014]
[21]Malebo HM,Tanja W,Cal M,Swaleh SAM,Omolo MO,Hassanali A,et al.Antiplasmodial,antitrypanosomal,antileshmanial and cytotoxicity activity of selected Tanzanian medicinal plants.Tanzan J Health Res 2009;11(4):226-34.
[22]Tiwari RK,Singh D,Singh J,Chhillar AK,Chandra R,Verma AK.Synthesis,antibacterial activity and QSAR studies of 1,2-disubstituted-