Scientific paper
Synthesis of Novel Linked Pyrazolyl-thiazolidinone Heterocycles as Potent Antibacterial Agents
Cherkupally Sanjeeva Reddy,1* Gaddam Rajesh Kumar,1 Macherla Vani Devi1 and Adki Nagaraj2
1	Department of Chemistry, University College, Kakatiya University, Warangal-506 009, India
2	Department of Pharmaceutical Chemistry, Telangana University, Nizamabad-503 322, India
* Corresponding author: E-mail: chsrkuc@yahoo.co.in Tel: +91-870-2573788, Fax:(off) +91-870-2439600
Received: 15-01-2011
Abstract
A novel series of 2-(3,5-dimethyl-1-phenyl-1^-4-pyrazolyl)-3-(aryl/heteroaryl)-1,3-thiazolidin-4-one derivatives 4a-h has been synthesized readily in one-pot from 3,5-dimethyl-1-phenyl-1_ff-4-pyrazolecarbaldehyde (3), and characterized via IR, NMR, MS and elemental analyses. Further, these compounds were screened for antibacterial (MIC) activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Staphylococcus pyogenes. Amongst them, compounds containing pyridyl 4g and pyrimidinyl 4h moiety exerted superior antibacterial activity against S. aureus and E. coli at the concentration of 6.25 |g/mL, which is less than the concentration of the standards neomycin and streptomycin, and emerged as potential molecules for further development.
Keywords: Thiazolan-4-one, pyrazole, antibacterial activity.
1. Introduction
Heterocyclic compounds represent one of the most active classes of compounds possessing a wide spectrum of biological activities, including antibacterial, antifungal, and other biological activities.1-6 Pyrazole and its derivatives represent one of the most active classes of compounds possessing a wide spectrum of biological activities such as antidepressant,7 inhibitors of protein kinases,8 antiagre-gating,9 antiarthritic,10 cerebroprotectors,11 antibacterial,12 antifungal,13 herbicidal,14 insecticidal15 and other biological activities.16-18 Some aryl pyrazoles were reported to have non-nucleoside HIV-1 reverse transcriptase inhibitory,19 COX-2 inhibitory activity,20 activation of the nitric oxide receptor and soluble guanylate cyclase activity.21 Similarly, there has been a considerable interest in the chemistry of thiazolidin-4-one ring system, which is a core structure in various synthetic pharmaceuticals displaying a broad spectrum of biological activities.22 Thiazolidin-4-one ring also occurs in nature; thus actithiazic acid isolated from streptomyces strains exhibits highly specific in
vitro activity against Mycobacterium tuberculosis.23 Thia-zolidin-4-one derivatives are also known to exhibit diverse bioactivities such as anti-convulsant,24 antidiarrheal,25 anti-platelet activating factor,26 anti-histaminic,27 antidiabetic,28 cyclooxygenase (COX) inhibitory,29 Ca2+-channel blocker,30 platelet activating factor (PAF) antagonist,31 cardioprotective,32 anti-ischemic,33 anti-cancer,34 tumor necrosis factor-a antagonist35 and nematicidal activities.36 The synthesis of heterocycles containing multi-structure in a molecule has received much attention in recent years.37 However, literature survey revealed that linked bi-heterocyclics containing pyrazole have seldom been reported.
In view of all these facts and as the continuation of our work on the synthesis of new heterocyclic derivati-ves,38-43 it was thought of interest to accommodate pyra-zole and thiazolidin-4-one moieties in a single molecular frame work and to obtain new heterocyclic compounds with potential biological activity. In the present study we report the synthesis and antibacterial evaluation of some new 2-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-3-(aryl/ heteroaryl)-1,3-thiazolan-4-one.
2. Results and Discussion
The P-diketones are excellent starting materials for the synthesis of pyrazole derivatives via the reaction of P-diketones 1 with phenylhydrazine under reflux in ethanol. This one-step method for the synthesis of the new 3,5-di-methyl-1-phenyl-1H-pyrazole (2) is carried out. The method is easy to perform and uses almost all the available starting material to give the product in high yield. Thus, heating an equimolar mixture of ethyl acetoacetate and phenylhydrazine in ethanol afforded 3,5-dimethyl-1-phenyl-1H-pyrazole (2) in 90% yield (Scheme 1). The elemental analysis and spectroscopic data are consistent with the assigned structure. IR spectrum of 2 exhibited absorption bands at 3010, 1630 and 1610 cm-1 due to C-H (aromatic), C=N and C=C of pyrazole ring, respectively. Its 1H NMR spectrum showed signals at S 7.10-7.20 (m, 5H, N-phenyl), 6.21 (s, 1H, pyrazole 4-H), 2.36 (s, 3H, 3-CH3) and 2.22 (s, 3H, 5-CH3).
Compound 2 has been utilized as a starting material for the synthesis of 3,5-dimethyl-1-phenyl-1H-4-pyrazo-lecarbaldehyde (3), thus compound 2 reacted with N,N-di-methylformamide (DMF) in the presence of phosphorous oxychloride to afford 3 in 86% yield (Scheme 1). The structure of 3 was confirmed with the elemental and spec-troscopic data. The IR spectrum of 3 revealed the appearance of carbonyl (C=O) band at 1700 cm-1 and formyl (C-H) band at 2854 cm-1. 1H NMR spectrum of compound 3 showed signals at S 9.98 (s, 1H, aldehyde proton), 7.25-7.15 (m, 5H, N-phenyl), 2.71 (s, 3H, 3-CH3) and 2.64 (s, 3H, 5-CH3). Further confirmation for the formation of compound 3 is obtained by the disappearance of the proton signal, corresponding to 4-position of the pyrazole ring.
The one-pot synthesis of 2-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-3-(aryl/heteroaryl)-1,3-thiazo-lidin-4-one derivatives 4a-h was carried out by the condensation-cyclization reaction between compound 3, primary aryl/heteroaryl amine and mercaptoacetic acid in the presence of ZnCl2 using dry toluene as the solvent under reflux for about 6 h (Scheme 1). The compounds, isolated by conventional work-up, were obtained in satisfactory yields. The elemental analyses and spectroscopic data are consistent with the assigned structures.
In the IR spectra of compounds 4a-h, disappearance of aldehyde (O=C-H) absorption band at about 2854 cm-1, which was present in compound 3, confirmed the formation of thiazolidin-4-one ring by the involvement of the aldehyde group. The absorption bands corresponding to C=N of the pyrazole ring and C=O of thiazoli-din-4-one ring were observed at about 1630 and 1710 cm-1, respectively. Further support was obtained from the 1H NMR spectra: the N-CH-S proton and 5-CH2 protons of thiazolidin-4-one ring appeared as singlets at S 5.64 and 3.73 ppm, respectively. These signals are further proof of evidence of their structures. The aromatic and aliphatic proton signals were observed at the expected regions. In summary, all the synthesized compounds exhibited satisfactory spectral data consistent with their structures.
3. Antibacterial Evaluation
The target compounds 4a-h were evaluated for their antibacterial activity against four representative organisms viz. Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Staphylococcus pyogenes by the tube dilution method recommended by National Committee for Clinical Laboratory Standards.44 Bacteria were grown overnight in Luria Bertani (LB) broth at 375 °C, harvested by centrifugation and then washed twice with sterile distilled water. Stock solutions of the series of compounds were prepared in DMSO. Each stock solution was diluted with standard method broth (Difco) to prepare serial twofold dilutions in the range of 100 to 0.8 pg/mL. Ten microliters of the broth containing about 105 colony-forming units (cfu)/mL of test bacteria were added to each well of a 96-well microtiter plate. Culture plates were incubated for 24 h at 37 °C, and the growth of bacteria was monitored visually and spectrophotometrically. Streptomycin and neomycin were also screened under identical conditions for comparison. The minimum inhibitory concentration (MIC, pg/mL, i.e. minimum concentration required to inhibit the growth of bacteria) of all the compounds was determined and observed that the compounds exhibited interesting biological activity with a degree of variation (Table 2).
Scheme 1. Synthetic route of 2-(3,5-dimethyl-1-phenyl-1ff-4-pyrazolyl)-3-(aryl/heteroaryl)-1,3-thiazolidin-4-ones
Table 1. Physical characterization of synthesized compounds 2-4
Product	Ar	Yield (%)	mp (oC)
2	-	90	270-272
3	-	86	124-126
4a	C6H5-	64	149-151
4b	4-CI-C6H4-	66	138-140
4c	4-(NO2)-C6H4-	71	143-145
4d	2-(CH3)-C6H4-	68	136-138
4e	4-(CH3)-C6H4-	70	139-141
4f	4-(OH)-C6H4-	72	151-153
4g	4-pyridyl	70	161-163
4h	2-pyrimidinyl	68	157-159
The antibacterial screening data revealed that all the tested compounds 4a-h are active and showed good antibacterial activity. Compounds, 4b, 4c, 4f, 4g, and 4h exhibited potent activity, compared to the standards, against all the microorganisms employed. The presence of 4-chlo-rophenyl 4b, 4-nitrophenyl 4c and 4-hydroxyphenyl 4f showed significant inhibition, which is more than the neomycin and equal to the streptomycin. Further, the compounds 4g and 4h showed excellent antibacterial activity against S. aureus and E. coli at the concentration less than the neomycin and streptomycin, therefore the presence of pyridyl group on nitrogen of thiazolidinone ring 4g and the presence of pirimidinyl ring 4h might be the reason for the significant inhibitory activity. The comparison of MIC values (pg/mL) of the 4g and 4h with the standards against different bacteria is presented in Figure 1.
Table 2. Antibacterial activity of compounds 4a-h
Minimum inhibitory concentration
		(MIC ^g/mL)		
Compound	B. subtilis	S. aureus	E. coli	S. pyogenes
4a	50.0	25.0	50.0	50.0
4b	12.5	12.5	25.0	12.5
4c	25.0	25.0	12.5	12.5
4d	25.0	50.0	25.0	25.0
4e	50.0	50.0	50.0	50.0
4f	12.5	12.5	12.5	25.0
4g	12.5	6.25	6.25	12.5
4h	12.5	12.5	6.25	12.5
neomycin	25.0	25.0	25.0	25.0
streptomycin	12.5	12.5	12.5	12.5
4. Experimental
Commercial grade reagents were used as supplied. Solvents except analytical reagent grade were dried and purified according to the literature when necessary. Reaction progress and purity checks of the compounds were
Fig. 1. Comparison of MIC values (ng/mL) of selected compounds and standard drugs
made by thin-layer chromatography (TLC) on pre-coated silica gel F254 plates from Merck and compounds visualized by exposure to UV light. Silica gel chromatographic columns (70-230 mesh) were used for separations. All the melting points are uncorrected and measured using Fisher-Johns apparatus. IR spectra were recorded as KBr disks on a Perkin-Elmer FTIR spectrometer. The 13C NMR spectra were recorded on a Varian Gemini spectrometer, operating at 300 and 75 MHz, respectively. Chemical shifts are expressed as ppm (5 values) against tetra-methylsilane (TMS) as internal standard and coupling constants (J) are reported in Hz units. Mass spectra were obtained on a VG micro mass 7070H spectrometer. Elemental analyses (C, H, N) determined by a Perkin-Elmer 240 CHN elemental analyzer, are within ± 0.4% of theoretical.
Preparation of 3,5-dimethyl-1-phenyl-1_ff-pyrazole
(2): A mixture of acetyl acetone 1 (1.95 g, 0.02 mol) and phenyl hydrazine hydrochloride (2.89 g, 0.02 mol) in et-hanol (20 mL) was heated under reflux for 3 h on a water bath. After completion of the reaction, ethanol was evaporated. The residue was poured in ice-cold water, neutralized with sodium bicarbonate and extracted with ether. The solvent was evaporated under reduced pressure to get the compound 2 as yellow-brown liquid; yield 90%; bp 270-272 °C; IR (KBr) i 3010, 2962, 1630, 1610 cm-1; 1H NMR (CDCl3): 5 2.22 (s, 3H, CH3), 2.36 (s, 3H, CH3), 6.21 (s, 1H, ArH), 7.10-7.20 (m, 5H, ArH); 13C NMR (CDCl3): 5 13.9, 14.6, 108.5, 123.4, 127.3, 129.0, 140.1, 141.7, 145.4; MS m/z: 172 (M+); Anal. Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.27. Found: C, 76.77; H, 6.95; N, 16.16.
Preparation of 3,5-dimethyl-1-phenyl-1_ff-4-pyrazole-carbaldehyde (3): To a cold N,N-dimethyl- formamide (1.55 mL, 0.02 mol), freshly distilled phosphorous oxych-loride (1.0 mL, 0.01 mol) was added with stirring over a period of 30 minutes. When formylation solution was obtained, a solution of compound 2 (1.72 g, 0.01 mol) in N,N-dimethylformamide (5 mL) was added drop wise,
while maintaining the temperature at 0-5 °C. The resulting mixture was heated under reflux for 1 h, cooled and poured with continuous stirring onto crushed ice and the obtained yellow precipitate was filtered off and recrystal-lized from aqueous ethanol to get the pure compound 3 as yellow solid; yield 86%; mp 124-126 °C. IR (KBr) i 3012, 2961, 2854, 1700, 1627, 1608 cm-1; 1H NMR (CDCl3): 5 2.64 (s, 3H, CH3), 2.71 (s, 3H, CH3), 7.157.25 (m, 5H, ArH), 9.98 (s, 1H, CHO); 13C NMR (CDCl3): 5 12.2, 14.4, 123.1, 127.0, 128.4, 129.4, 139.5, 145.7, 151.5, 182.3; MS m/z: 200 (M+); Anal. Calcd for C12H12N2O: C, 71.98; H, 6.04; N, 13.99. Found: C, 71.94;
H,	6.00; N, 14.02.
General procedure for synthesis of 2-(3,5-dimethyl-1-phenyl-1ff-4-pyrazolyl)-3-(aryl)-1,3-thiazolidin-4-ones 4a-h: To a stirred mixture of compound 3 (2.0 g, 0.01 mol), aryl/heteroaryl amine (0.01 mol) and thioglycolic acid (1.85 g, 0.02 mol) in dry toluene (10 mL), ZnCl2 (1.36 g, 0.01 mol) was added and refluxed at 110 °C for 6 h. After cooling, the filtrate was concentrated to dryness under reduced pressure and the residue was taken-up in ethyl acetate. The ethyl acetate layer was washed with brine, 5% sodium bicarbonate solution and finally with brine. The organic layer was dried over Na2SO4 and evaporated to dryness at reduced pressure. The crude product thus obtained was purified by column chromatography on silica gel with hexane-ethyl acetate as eluent to afford pure compounds 4a-h.
2-(3,5-Dimethyl-1-phenyl-1ff-4-pyrazolyl)-3-phenyl-
I,3-thiazolidin-4-one	(4a). Yield 64%; mp 149-151 °C; IR (KBr) i 3032, 2965, 1710, 1624, 1600, 1518, 746 cm-1; 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.0(3-7.25 (m, 10H, ArH); 13C NMR (DMSO-d6): 5 11.4, 14.2, 36.6, 52.4, 115.2, 122.3, 124.3, 127.1, 1277.8, 128.0, 128.9, 129.0, 137.3, 139.2, 151.1, 175.1; MS m/z: 350 (M++1); Anal. Calcd for C20H19N3OS: C, 68.74; H, 5.48; N, 12.02. Found: C, 68.70; H, 5.42; N, 12.08.
3-(4-Chlorophenyl)-2-(3,5-dimethyl-1-phenyl-1#-4-pyrazolyl)-1,3-thiazolidin-4-one (4b). Yield 66%; mp 138-140 °C; IR (KBr) i 3032, 2961, 1712, 1624, 1605, 1510, 748, 685 cm-1; 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.00-7.25 (m, 7H, ArH), 7.86 (d, J = 8.7 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.4, 14.2, 36.6, 52.3,
115.2,	122.6, 124.6, 127.1, 1267.8, 128.9, 129.8, 131.6,
137.3,	139.1, 151.0, 174.1; MS m/z: 383 (M+); Anal. Calcd for C20H18ClN3OS: C, 62.57; H, 4.73; N, 10.95. Found: C, 62.60; H, 4.75; N, 10.91.
2-(3,5-Dimethyl-1-phenyl-1ff-4-pyrazolyl)-3-(4-nitro-phenyl)-1,3-thiazolidin-4-one (4c). Yield 71%; mp 143-145 °C; IR (KBr) i 3032, 2961, 1710, 1627, 1604,
1557, 1342, 749 cm-1. 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s,
IH,	S-CH-N), 7.00-7.20 (m, 5H, ArH), 7.82 (d, J = 8.8 Hz, 2H, ArH), 8.10 (d, J = 8.8 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.3, 14.1, 36.6, 52.3, 115.2, 122.5, 124.4, 127.8, 128.1, 128.9, 133.2, 137.3, 139.3, 144.2, 150.7, 174.2; MS m/z: 394 (M+); Anal. Calcd for C20H18N4O3S: C, 60.90; H, 4.60; N, 14.20. Found: C, 60.83; H, 4.64; N, 14.15.
2-(3,5-Dimethyl-1-phenyl-1_ff-4-pyrazolyl)-3-(2-me-thylphenyl)-1,3-thiazolidin-4-one (4d). Yield 68%; mp 136-138 °C; IR (KBr) i 3035, 2962, 1710, 1625, 1602, 748 cm-1; 1H NMR (DMSO-d6): 5 2.14 (s, 3H, CH3), 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.10-7.35 (m, 9H, ArH); 13C NMR (DMSO-d6): 5 11.2, 14.0, 18.2, 36.0, 50.7, 115.3, 122.4, 125.3, 126.6, 127.0, 127.8, 128.1, 128.8, 131.2, 133.4,
137.3,	139.1, 150.7, 173.6; MS m/z: 364 (M++1); Anal. Calcd for C21H21N3OS: C, 69.39; H, 5.82; N, 11.56. Found: C, 69.33; H, 5.80; N, 11.61.
2-(3,5-Dimethyl-1-phenyl-1_ff-4-pyrazolyl)-3-(4-me-thylphenyl)-1,3-thiazolidin-4-one (4e). Yield 70%; mp 139-141 °C; IR (KBr) i 3032, 2965, 1710, 1626, 1602, 746 cm-1; 1H NMR (DMSO-d6): 5 2.11 (s, 3H, CH3), 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.10-7.30 (m, 7H, ArH), 7.54 (d, J = 8.2 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.3, 14.1, 22.6, 36.4, 52.3, 115.0, 118.2, 122.5, 126.6, 127.8, 128.8,
129.4,	136.8, 137.2, 139.1, 151.0, 174.2; MS m/z: 363 (M+); Anal. Calcd for C21H21N3OS: C, 69.39; H, 5.82; N,
II.56.	Found: C, 69.40; H, 5.58; N, 11.51.
2-(3,5-Dimethyl-1-phenyl-1_ff-4-pyrazolyl)-3-(4-hydro-xyphenyl)-1,3-thiazolidin-4-one (4f). Yield 72%; mp 151-153 °C; IR (KBr) i 3375, 3032, 1710, 1630, 1604, 745 cm-1; 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 6.21 (s, 1H OH), 6.91 (d, J = 8.6 Hz, 2H, ArH), 7.10-7.25 (m, 5H, ArH), 7.49 (d, J = 8.6 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.2, 14.2, 36.4, 51.4, 115.0, 118.2, 120.7, 122.0, 122.4, 127.8, 128.8, 137.1, 139.0, 151.0, 152.7, 174.2; MS m/z: 366 (M++1); Anal. Calcd for C20H19N3O2S: C, 65.73; H, 5.24; N, 11.50. Found: C, 6576; H 5.19; N, 11.42.
2-(3,5-Dimethyl-1-phenyl-1_ff-4-pyrazolyl)-3-(4-pyri-dyl)-1,3-thiazolidin-4-one (4g). Yield 70%; mp 161-163 °C; IR (KBr) i 3018, 2910, 1710, 1627, 1600, 1595, 746 cm-1; 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.05-7.20 (m, 5H, ArH), 7.36 (d, J = 5.9 Hz, 2H, ArH), 8.05 (d, J = 5.9 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.4, 14.2, 36.7, 52.0, 113.7, 115.1, 122.6, 127.8, 1268.8, 137.2, 139.1, 140.1, 151.1, 152.0, 174.3; MS m/z: 350
(M+); Anal. Calcd for C19H18N4OS: C, 65.12; H, 5.18; N, 15.99. Found: C, 65.06; H, 5.234; N, 15.92.
2-(3,5-Dimethyl-1-phenyl-1_ff-4-pyrazolyl)-3-(2-pyri-midinyl)-1,3-thiazolidin-4-one (4h). Yield 68%; mp 157-159 °C; IR (KBr) i 3020, 2942, 1710, 1630, 1600, 1595, 749 cm-1; 1H NMR (DMSO-d6): 5 2.27 (s, 3H, CH3), 2.34 (s, 3H, CH3), 3.73 (s, 2H, CH2-S), 5.64 (s, 1H, S-CH-N), 7.10-7.25 (m, 7H, ArH), 8.52 (d, J = 5.6 Hz, 2H, ArH); 13C NMR (DMSO-d6): 5 11.4, 14.2, 36.0, 50.7, 115.1, 117.5, 122.5, 127.8, 128.8, 137.2, 139.1, 146.7, 151.1, 159.0, 172.7; MS m/z: 352 (M++1); Anal. Calcd for C18H17N5OS: C, 61.52; H, 4.88; N, 19.94. Found: C, 61.56; H, 4.81; N, 19.87.
5. Conclusions
A series of novel 2-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-3-(aryl/heteroaryl)-1,3-thiazolidin-4-one derivatives 4a-h has been synthesized readily in one-pot from the 3,5-dimethyl-1-phenyl-1H-4-pyrazolecarbaldehyde 3 and evaluated their antibacterial activity against various bacteria. The compounds containing pyridyl 4g and pyri-midinyl 4h moiety showed enhanced antibacterial activity against S. aureus and E. coli at the concentration less than both the standards neomycin and streptomycin and emerged as potential molecules for further development.
6. Acknowledgements
The authors are grateful to the Director, Indian Institute of Chemical Technology, Hyderabad, India, for providing NMR and Mass spectral data. Financial assistance from the UGC SAP (Phase-I)-DRS Programme, New Delhi, India, is greatly acknowledged.
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Povzetek
Z »one-pot« sintezo smo iz 1-fenil-3,5-dimetil-1^-4-pirazolkarbaldehida (3) pripravili serijo novih derivatov 2-(1-fenil-3,5-dimetil-1ff-4-pirazolil)-3-(aril/heteroaril)-1,3-tiazolidin-4-onov 4a-h ter jih analizirali z IR, NMR, MS in element-no analizo. Tem spojinam smo določili antibakterijsko delovanje (MIC) proti Bacillus subtilis, Staphylococcus aureus, Escherichia coli in Staphylococcus pyogenes. Med novimi spojinami sta spojini, ki vsebujeta piridilno 4g in pirimidinil-no 4h skupino, pokazali odlično antibakterijsko delovanje proti S. aureus in E. coli že pri koncentracijah 6.25 |g/mL, kar je manj, kot so bile potrebne koncentracije standardnih spojin (neomcin in streptomcin); s tem sta se ti dve izkazali kot možni potencialni spojini za nadaljnje predelave.