In vitro antibacterial activity of ten series of substituted quinazolines

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Table 4. Antibacterial activity of 2,6-disubstituted 4-anilinoquinazolines. a X N R HN N Y No. X R Y E. coli b P. aeruginosa b S. aureus b B. subtilis b 84 6-Br 2-Diethylamino 4’-NO2 >500 >500 >500 10500 >500 >500 86 6-Br 2-Morpholin-4-yl 4’-Br >500 >500 >500 >500 87 6-Br 2-Morpholin-4-yl 2’-NO2 >500 >500 >500 >500 88 6-Br 2-Morpholin-4-yl 4’-NO2 >500 >500 >500 >500 89 6-Br 2-Morpholin-4-yl H >500 >500 >500 >500 90 H Morpholin-4-yl 4’-Br >500 >500 >500 >500 91 6-Cl Morpholin-4-yl 4’-NO2 >500 >500 >500 >500 92 H Phenyl H >500 >500 10** 10500 1500 95 6-Cl Phenyl 4’-CH3 >500 >500 >500 >500 Amp 1** >500 0.04** 10** a Values of MIC are in mg/L; Amp-ampicillin; ** bactericidal effect, * bacteriostatic effect. b Reported in JANTOVÁ et al. (1994a). Table. 5 Antibacterial activity of some [1,2,4]triazolo[4,3-c]quinazolines. a X N R N N N Z No. X R Z E. coli P. aeruginosa S. aureus B. subtilis 96 9-Cl Morpholin-4-yl NH-phenyl 10–100 10–100 10–100 10–100 97 9-Cl Piperidin-1-yl NH-phenyl 10–100 10–100 10–100 10–100 98 9-Cl 4-Phenylpiperazin-1-yl NH-phenyl >200 >200 >200 >200 99 7-Me Phenyl NH-phenyl >200 >200 >200 >200 100 9-Cl Morpholin-4-yl Indol-3-yl >100 >100 100** 100** 101 9-Cl Morpholin-4-yl 5-nitrothiophen-2-yll >100 >100 50** 10** 102 9-Cl Morpholin-4-yl 5-nitrofuran-2-yl >100 >100 50** 10** 103 9-Cl Morpholin-4-yl 5-phenylsulfonylfuran-2-yl >100 >100 >100 >100 104 9-Cl Morpholin-4-yl 2-acetylfuran-2-yl >100 >100 >100 >100 105 9-Cl Morpholin-4-yl 5-bromofuran-2-yl >100 >100 100* 50* 106 9-Cl Morpholin-4-yl 4-acetamidophenyl >100 >100 >100 >100 107 9-Cl Morpholin-4-yl 2-nitrophenyl >100 >100 >100 >100 108 9-Cl Morpholin-4-yl 2-chlorophenyl >100 >100 >100 >100 109 9-Cl 4-Phenylpiperazin-1-yl 4-chlorophenyl >100 >100 >100 >100 110 9-Cl 4-Phenylpiperazin-1-yl 5-nitrofuran-2-yl >100 >100 100** 50** 111 9-Cl 4-Phenylpiperazin-1-yl 5-chlorofuran-2-yl >100 >100 >100 >100 112 9-Cl 4-Phenylpiperazin-1-yl furan-2-yl >100 >100 >100 >100 113 9-Cl 4-Phenylpiperazin-1-yl 5-bromofuran-2-yl >100 >100 >100 >100 114 9-Cl 4-Phenylpiperazin-1-yl phenyl >100 >100 >100 >100 115 9-Cl 4-Phenylpiperazin-1-yl 4-N,N-dimethylaminophenyl >100 >100 >100 >100 Amp 1** >500 0.04** 10** a Values of MIC are in mg/L; Amp-ampicillin; ** bactericidal effect. 746
Table 6. Antibacterial activity of some 1-(alkyl/aryl-amino)-10H-[1,2,4]triazino[5,4-b] quinazolin-10-ones. a N N N N O HN R No. R E. coli P. aeruginosa S. aureus B. subtilis 116 Phenyl 5* >100 25* 1** 117 4-chlorophenyl 10* >100 100* 5* 118 2-nitrophenyl 5* >100 25* 1* 119 3-hydroxyphenyl >100 >100 >100 >100 120 3-methylphenyl 5* 100* 10* 1** 121 isopropyl 10** >100 25* 1** Amp 1** >100 0.04** 10** a Values of MIC are in mg/L; Amp-ampicillin; ** bactericidal effect, * bacteriostatic effect. effective against B. subtilis and S. aureus. Derivative 84 influenced only Gram positiveB. subtilis. Table 5 shows the activity of substituted 1,2,4-triazolo[4,3-c]quinazolines. The broadest antibacterial spectrum was demonstrated with derivatives 96 and 97 which were effective with all the tested bacteria. Derivatives 100, 101, 102, 105 and 110 influenced Gram positive S. aureus and B. subtilis. The MIC values of these derivatives exerted bactericidal effect on Gram positive bacteria. The effect of derivatives 101 and 102 on B. subtilis was the same as that of ampicillin. Minimal inhibition concentration (10 mg/L) exhibited bactericidal effect. The MIC values of the 10H-[1,2,4]triazino[5, 4-b]quinazolin-10-ones against Gram positive and Gram negative bacteria is shown in Table 6. Five derivatives (116, 117, 118, 120, 121) were effective on the three bacterial strains tested. The highest activity of these compounds was against B. subtilis. A concentration of 1 mg/L of 118 induced 100% inhibition of the bacterial growth. On the other hand, the concentration of derivatives 116, 120 and 121 exhibited bactericidal effect against B. subtilis. The MIC values for B. subtilis was 2-times (for derivative 117) and 10-times (for derivatives 116, 118, 120 and 121) lower than the corresponding value for ampicillin. Derivative 120 exhibited the highest antibacterial activity on S. aureus (MIC = 10 mg/L). A certain antibacterial effect on S. aureus was manifested by derivatives 116, 118, and 121, too (MIC = 25 mg/L). Derivatives 116, 118 and 120 demonstrated the highest antibacterial activity on E. coli (MIC = 5 mg/L). Minimal inhibition concentration of derivative 121 was 10 mg/L and it was also the concentration which induced bactericidal effect on E. coli. The least sensitive to the effect of 10H-[1,2,4]triazino[5,4-b]quinazolin-10-ones was P. aeruginosa. Only derivative 120 exhibited the total inhibition of the growth of P. aeruginosa (MIC = 100 mg/L). Other 10H-[1,2,4]triazino[5,4b]quinazolin-10-ones were inactive. ThedatapresentedinTable7showtheantibacterial activity of quinazoline derivatives comprising amino acid moiety at position 3. All the test compounds were found to be non-effective. The MIC values were higher than the highest concentration tested. The effect of [1,2,4]triazoloquinazolines is summarized in Table 8. The broadest antibacterial spectrum was encountered with derivative 142 which was effective with all tested bacteria (MIC = 10-100 mg/L). Derivative 140 was effective with the three tested bacteria. It was more active against S. aureus and E. coli than ampicillin. Derivative 142 was more active against P. aeruginosa than ampicillin. S. aureus was found to be the most sensitive bacterium towards the quinazolines presented in Table 8. Derivatives 140, 142, 144 and 145 manifested antibacterial activity on S. aureus. The MIC values of tetrazolo[1,5-c]quinazolines are given in Table 9. Sensitivity of Gram positive bacteria to the derivatives was higher than that of Gram negative bacteria. Derivative 155 was effective against S. aureus and P. aeruginosa (MIC= 1000 mg/L). None of tetrazolo[1,5c]quinazolines influenced E. coli. The results presented in Table 10 show the antibacterial activity of the two triazino[4,3c]quinazolines. None of them influenced the bacterial growth (MIC > 100 mg/L). The data presented in Tables 1–10 imply 747
Page 1 and 2: Biologia, Bratislava, 59/6: 741—7
Page 3 and 4: Table 1. Antibacterial effect of 2-
Page 5: Table 3. Antibacterial activity of
Page 9 and 10: Table 9. Antibacterial activity of
Page 11 and 12: BODAJLA, M.,STANKOVSKÝ, Š.,ŠPIRK

In vitro antibacterial activity of ten series of substituted quinazolines

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