1-R-2-([1,2,4] Triazolo[1,5-c] quinazoline-2-ylthio) etanon(ol) s: Synthesis, Bioluminescence Inhibition, Molecular Docking Studies, Antibacterial and Antifungal Activities

被引:11
作者
Antypenko, Lyudmyla M. [1 ]
Kovalenko, Sergiy I. [1 ]
Karpenko, Oleksandr V. [2 ]
Katsev, Andrew M. [3 ]
Novikov, Volodymyr P. [4 ]
Fedyunina, Natalia S. [5 ]
机构
[1] Zaporizhzhya State Med Univ, Organ & Bioorgan Chem Dept, 26 Mayakovsky Ave, UA-69035 Zaporizhzhya, Ukraine
[2] Enamine Ltd, Kiev, Ukraine
[3] VI Vernadsky Crimean Fed Univ, Dept Med & Pharmaceut Chem, Simferopol, Ukraine
[4] Lviv Polytech Natl Univ, Pharm & Biotechnol Dept, Technol Biol Act Subst, Lvov, Ukraine
[5] Zaporizhzhya Reg Hosp, Bacterial Lab, Zaporizhzhya, Ukraine
关键词
Antibacterial; antifungal; bioluminescence inhibition; 1-R-2-([1,2,4]triazolo[1,5-c]quinazoline-2-ylthio)etanon(ol)s;
D O I
10.2174/1573409912666160126142236
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The increasing mortality due to antibacterial resistance necessitates the search for novel antimicrobial agents. Hence, series of 1-R-2-([1,2,4]triazolo[1,5-c]quinazoline-2-ylthio) etanon(ol) s were synthesized, evaluated by spectral data and studied against St. aureus, M. luteum, E. faecalis, E. aerogenes, P. aeruginosa, C. sakazakii, E. coli, K. pneumonia, hospital Streptococcus spp., C. albicans and A. niger in 100, 500 mu g/mL and 100 mu g/disk. Substances exhibited moderate toxicity in 0.025, 0.1 and 0.25 mg/mL in bioluminescence inhibition tests of Photobacterium leiognathi. SAR exposed that introduction of 2,4-(Cl)(2)C6H3-, 2,5-(OMe)(2)C6H3-, 4-Me-2-iPr-C6H3O-and 3-iPr-C6H4O-fragments and reduction of the pyrimidine ring of R-([1,2,4] triazolo[1,5-c] quinazolin-2-ylthio) alcohols were the best modifications to promote antimicrobial activity. Molecular docking showed their good affinity into the active sites of EcPanK-AMPPNP and hDHFR. Hence, reported results will be used for subsequent QSAR model creation and purposeful antimicrobial modification of the strongest compounds.
引用
收藏
页码:29 / 41
页数:13
相关论文
共 20 条
[1]  
Alvarez J., 2005, VIRTUAL SCREENING DR
[2]  
[Anonymous], 2009, FRED RECEPTOR2 2 5 V
[3]   Synthesis of New 2-Thio-[1,2,4]triazolo[1,5-c]quinazoline Derivatives and Its Antimicrobial Activity [J].
Antipenko, Lyudmila ;
Karpenko, Alexander ;
Kovalenko, Sergey ;
Katsev, Andrew ;
Komarovska-Porokhnyavets, Elena ;
Novikov, Vladimir ;
Chekotilo, Aleksey .
CHEMICAL & PHARMACEUTICAL BULLETIN, 2009, 57 (06) :580-585
[4]   Synthesis, Cytotoxicity by Bioluminescence Inhibition, Antibacterial and Antifungal Activity of ([1,2,4]Triazolo[1,5-c]quinazolin-2-ylthio)carboxylic Acid Amides [J].
Antipenko, Lyudmila N. ;
Karpenko, Alexander V. ;
Kovalenko, Sergey I. ;
Katsev, Andrew M. ;
Komarovska-Porokhnyavets, Elena Z. ;
Novikov, Vladimir P. .
ARCHIV DER PHARMAZIE, 2009, 342 (11) :651-662
[5]  
Antypenko Lyudmyla M, 2013, Sci Pharm, V81, P15, DOI 10.3797/scipharm.1208-13
[6]  
Arooj M., 2014, MOL STIMUL, P1
[7]   Fluoroboric acid adsorbed on silica gel catalyzed regioselective ring opening of epoxides with nitrogen heterocycles [J].
Bandgar, B. P. ;
Patil, Abasaheb V. .
TETRAHEDRON LETTERS, 2007, 48 (01) :173-176
[8]  
Binaeian E., 2013, INT J CHEM MOL NUCL, V7, P280
[9]   Structural and Biochemical Characterization of Compounds Inhibiting Mycobacterium tuberculosis Pantothenate Kinase [J].
Bjorkelid, Christofer ;
Bergfors, Terese ;
Raichurkar, Anand Kumar V. ;
Mukherjee, Kakoli ;
Malolanarasimhan, Krishnan ;
Bandodkar, Balachandra ;
Jones, T. Alwyn .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (25) :18260-18270
[10]  
Escher B, 2012, BIOANALYTICAL TOOLS IN WATER QUALITY ASSESSMENT, P1