新型1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成、抗菌活性及与FabⅠ作用的分子模拟
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摘要
以3-芳基/烷基-4-氨基-5-巯基-1,2,4-三唑为原料,经过环化和糖化反应,设计合成了10个未见报道的化合物3-芳基/烷基-6-S-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑(3a~3j),其结构经核磁共振波谱、高分辨质谱和红外光谱确认.生物活性测试表明,所有化合物均对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念株菌表现出一定的抗菌活性,其中化合物3c对4种测试菌株的最小抑菌浓度(MIC)最低,且接近于氟康唑的参照数据,具有较强的抗菌活性.利用Auto Dock 4.0程序研究了目标化合物3a~3j与大肠杆菌FabⅠ受体蛋白分子的相互作用和结合自由能变化规律.
Ten novel compounds of 3-alkyl / aryl-6-S-( 2',3',4',6'-tetra-O-acetyl-β-D-glcopyranosyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were designed and synthesized from 3-alkyl / aryl-4-amino-5-mercapto-1,2,4-triazoles. The structures of all the compounds were confirmed by means of1 H NMR,13 C NMR,HRMS and IR. The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities on Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Monilia albican. Especially,the compound 3c had strong antibacterial by the lowest minimal inhibitory concentration( MIC) values on the four tested strains which were close to those of the controlled drug fluconazole. The interaction and binding free energy of the target compounds( 3a—3j) with FabⅠ were studied by Auto Dock 4.0.
Ten novel compounds of 3-alkyl / aryl-6-S-( 2',3',4',6'-tetra-O-acetyl-β-D-glcopyranosyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were designed and synthesized from 3-alkyl / aryl-4-amino-5-mercapto-1,2,4-triazoles. The structures of all the compounds were confirmed by means of1 H NMR,13 C NMR,HRMS and IR. The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities on Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Monilia albican. Especially,the compound 3c had strong antibacterial by the lowest minimal inhibitory concentration( MIC) values on the four tested strains which were close to those of the controlled drug fluconazole. The interaction and binding free energy of the target compounds( 3a—3j) with FabⅠ were studied by Auto Dock 4.0.
引文
[1]Almajan G.L.,Barbuceanu S.F.,Bancescu G.,Saramet I.,Saramet G.,Draghici C.,European Journal of Medicinal Chemistry,2010,45(12),6139—6146
[2]Husain A.,Rashid M.,Akhter A.,Journal of Pharmacy Research,2011,4(3),888—890
[3]Li Y.D.,Mao W.T.,Fan Z.J.,Li J.J.,Fang Z.,Ji X.T.,Zong G.N.,Li F.Y.,Chem.Res.Chinese Universities,2014,30(3),390—395
[4]Peng C.Y.,Lu J.R.,Xin C.W.,Li J.F.,Ji D.,Bao X.R.,Chem.J.Chinese Universities,2013,34(6),1394—1402(彭春勇,卢俊瑞,辛春伟,李建发,戢丹,鲍秀荣.高等学校化学学报,2013,34(6),1394—1402)
[5]Rajesh D.H.,Satyanarayana D.,Int.J.Pharm.Bio.Sci.,2012,3(4),183—192
[6]Mahendra S.,Rajesh K.,Indian Journal of Chemistry,2006,4(5),1009—1013
[7]Sadaf J.G.,Suroor A.K.,Nadeem S.,Medicinal Chemistry Letters,2010,20(16),4762—4765
[8]Gita C.,Umesh K.,Sandhya B.,Jagdish K.,Journal of Enzyme Inhibition and Medicinal Chemistry,2012,27(5),658—665
[9]Mohd A.,Kumar H.,Javed S.A.,European Journal of Medicinal Chemistry,2008,43(10),2056—66
[10]Zhao J.,Xuan L.N.,Zhao H.C.,Cheng J.,Fu X.Y.,Li S.,Jing F.,Liu Y.M.,Chen B.Q.,Chem.Res.Chinese Universities,2014,30(5),764—769
[11]Ibrahim D.A.,European Journal of Medicinal Chemistry,2009,44(7),2776—2781
[12]Asif H.,Mohammad A.N.,Mohammad S.,Acta Poloniae Pharmaceutica,2009,66(2),135—140
[13]Feng Z.N.,Lu J.R.,Xin C.W.,Li J.F.,Bao X.R.,Zhang T.T.,Chem.J.Chinese Universities,2013,34(5),1143—1150(冯钟念,卢俊瑞,辛春伟,李建发,鲍秀容,张彤彤.高等学校化学学报,2013,34(5),1143—1150)
[14]Driguez H.,Chem.Bio.Chem.,2001,2(5),311—318
[15]Knapp S.,Gonzalez S.,Myers D.S.,Eekinan L.L.,Bewley C.A.,Org.Lett.,2002,4(24),4337—4339
[16]Jahn M.,Marles J.,Warren R.A.,Withers S.G.,Angew.Chem.Int.Ed.,2003,42(3),352—354
[17]Uhrig M.L.,Manzano V.E.,Varela O.,Eur.J.Org.Chem.,2006,2006(1),162—168
[18]Mu M.M.,Lu B.W.,Lu J.R.,Xin C.W.,Ji D.,Li J.F.,Bao X.R.,Chinese Journal of Organic Chemistry,2012,32,1101—1107(穆曼曼,卢博为,卢俊瑞,辛春伟,戢丹,李建发,鲍秀荣.有机化学,2012,32,1101—1107)
[19]Zhao Q.,Lu J.R.,Xin C.W.,Bao X.R.,Gao H.Y.,Zhao X.,Li S.,Rui T.T.,Chem.J.Chinese Universities,2011,32(12),2806—2811(赵芡,卢俊瑞,辛春伟,鲍秀荣,高海燕,赵旭,李莎,芮甜甜.高等学校化学学报,2011,32(12),2806—2811)
[20]Peng C.Y.,Lu J.R.,Xin C.W.,Li J.F.,Ji D.,Bao X.R.,Chinese Journal of Organic Chemistry,2013,33,383—388(彭春勇,卢俊瑞,辛春伟,李建发,戢丹,鲍秀荣.有机化学,2013,33,383—388)
[21]Ai Y.X.,Lu J.R.,Xin C.W.,Mu J.B.,Yang X.Y.,Zhang H.,Acta Phys.Chim.Sin.,2014,30(3),559—568(艾义新,卢俊瑞,辛春伟,穆江蓓,杨旭云,张贺.物理化学学报,2014,30(3),559—568)
[22]Ling X.L.,Journal of Luoyang Normal University,2008,(2),75—77(凌勋利.洛阳师范学院学报,2008,(2),75—77)
[23]Karegoudar P.,Prasad D.J.,Ashok M.,Mahalinga M.,Poojary B.,Holla B.S.,European Journal of Medicinal Chemistry,2008,43,808—815
[24]Liu C.Y.,Zhao Q.Q.,Li J.,Chemical Reagents,2001,23(6),344—345(柳翠英,赵全芹,李娟.化学试剂,2001,23(6),344—345)
[25]Eweiss N.F.,Bahajaj A.A.,Journal of Heterocyclic Chemistry,1987,24(4),1173—1182
[26]Mohan J.,Indian Journal of Chemistry,Section B,2005,44B(3),628—630
[27]Potts K.T.,Huseby R.M.,Chemistry&Industry(London,United Kingdom),1964,46,1919—1920
[28]Ji D.,Lu J.R.,Lu B.W.,Xin C.W.,Mu J.B.,Li J.F.,Peng C.Y.,Bao X.R.,Bioorganic&Medicinal Chemistry Letters,2013,23,1997—2000
[2]Husain A.,Rashid M.,Akhter A.,Journal of Pharmacy Research,2011,4(3),888—890
[3]Li Y.D.,Mao W.T.,Fan Z.J.,Li J.J.,Fang Z.,Ji X.T.,Zong G.N.,Li F.Y.,Chem.Res.Chinese Universities,2014,30(3),390—395
[4]Peng C.Y.,Lu J.R.,Xin C.W.,Li J.F.,Ji D.,Bao X.R.,Chem.J.Chinese Universities,2013,34(6),1394—1402(彭春勇,卢俊瑞,辛春伟,李建发,戢丹,鲍秀荣.高等学校化学学报,2013,34(6),1394—1402)
[5]Rajesh D.H.,Satyanarayana D.,Int.J.Pharm.Bio.Sci.,2012,3(4),183—192
[6]Mahendra S.,Rajesh K.,Indian Journal of Chemistry,2006,4(5),1009—1013
[7]Sadaf J.G.,Suroor A.K.,Nadeem S.,Medicinal Chemistry Letters,2010,20(16),4762—4765
[8]Gita C.,Umesh K.,Sandhya B.,Jagdish K.,Journal of Enzyme Inhibition and Medicinal Chemistry,2012,27(5),658—665
[9]Mohd A.,Kumar H.,Javed S.A.,European Journal of Medicinal Chemistry,2008,43(10),2056—66
[10]Zhao J.,Xuan L.N.,Zhao H.C.,Cheng J.,Fu X.Y.,Li S.,Jing F.,Liu Y.M.,Chen B.Q.,Chem.Res.Chinese Universities,2014,30(5),764—769
[11]Ibrahim D.A.,European Journal of Medicinal Chemistry,2009,44(7),2776—2781
[12]Asif H.,Mohammad A.N.,Mohammad S.,Acta Poloniae Pharmaceutica,2009,66(2),135—140
[13]Feng Z.N.,Lu J.R.,Xin C.W.,Li J.F.,Bao X.R.,Zhang T.T.,Chem.J.Chinese Universities,2013,34(5),1143—1150(冯钟念,卢俊瑞,辛春伟,李建发,鲍秀容,张彤彤.高等学校化学学报,2013,34(5),1143—1150)
[14]Driguez H.,Chem.Bio.Chem.,2001,2(5),311—318
[15]Knapp S.,Gonzalez S.,Myers D.S.,Eekinan L.L.,Bewley C.A.,Org.Lett.,2002,4(24),4337—4339
[16]Jahn M.,Marles J.,Warren R.A.,Withers S.G.,Angew.Chem.Int.Ed.,2003,42(3),352—354
[17]Uhrig M.L.,Manzano V.E.,Varela O.,Eur.J.Org.Chem.,2006,2006(1),162—168
[18]Mu M.M.,Lu B.W.,Lu J.R.,Xin C.W.,Ji D.,Li J.F.,Bao X.R.,Chinese Journal of Organic Chemistry,2012,32,1101—1107(穆曼曼,卢博为,卢俊瑞,辛春伟,戢丹,李建发,鲍秀荣.有机化学,2012,32,1101—1107)
[19]Zhao Q.,Lu J.R.,Xin C.W.,Bao X.R.,Gao H.Y.,Zhao X.,Li S.,Rui T.T.,Chem.J.Chinese Universities,2011,32(12),2806—2811(赵芡,卢俊瑞,辛春伟,鲍秀荣,高海燕,赵旭,李莎,芮甜甜.高等学校化学学报,2011,32(12),2806—2811)
[20]Peng C.Y.,Lu J.R.,Xin C.W.,Li J.F.,Ji D.,Bao X.R.,Chinese Journal of Organic Chemistry,2013,33,383—388(彭春勇,卢俊瑞,辛春伟,李建发,戢丹,鲍秀荣.有机化学,2013,33,383—388)
[21]Ai Y.X.,Lu J.R.,Xin C.W.,Mu J.B.,Yang X.Y.,Zhang H.,Acta Phys.Chim.Sin.,2014,30(3),559—568(艾义新,卢俊瑞,辛春伟,穆江蓓,杨旭云,张贺.物理化学学报,2014,30(3),559—568)
[22]Ling X.L.,Journal of Luoyang Normal University,2008,(2),75—77(凌勋利.洛阳师范学院学报,2008,(2),75—77)
[23]Karegoudar P.,Prasad D.J.,Ashok M.,Mahalinga M.,Poojary B.,Holla B.S.,European Journal of Medicinal Chemistry,2008,43,808—815
[24]Liu C.Y.,Zhao Q.Q.,Li J.,Chemical Reagents,2001,23(6),344—345(柳翠英,赵全芹,李娟.化学试剂,2001,23(6),344—345)
[25]Eweiss N.F.,Bahajaj A.A.,Journal of Heterocyclic Chemistry,1987,24(4),1173—1182
[26]Mohan J.,Indian Journal of Chemistry,Section B,2005,44B(3),628—630
[27]Potts K.T.,Huseby R.M.,Chemistry&Industry(London,United Kingdom),1964,46,1919—1920
[28]Ji D.,Lu J.R.,Lu B.W.,Xin C.W.,Mu J.B.,Li J.F.,Peng C.Y.,Bao X.R.,Bioorganic&Medicinal Chemistry Letters,2013,23,1997—2000