MEDICINAL CHEMISTRY RESEARCH
Med Chem Res (2012) 21:4455–4462 DOI 10.1007/s00044-012-9986-0
ORIGINAL RESEARCH
Promising trend for amendment of drug molecule against resist pathogens: synthesis, characterization, and application Ripul Mehrotra • Satyendra N. Shukla Pratiksha Gaur
•
Received: 19 December 2010 / Accepted: 27 January 2012 / Published online: 17 February 2012 Ó Springer Science+Business Media, LLC 2012
Abstract It has been observed that antibiotic susceptibility against several bacterial strains varies with time and environment. The widespread drug resistance against pathogens in our environment stresses the need for regular monitoring of antibiotics’ susceptibility, and developing a new design being active against resist pathogens. In this study, a Schiff base derivative of Ofloxacin has been synthesized and characterized by FT-IR, 1H-NMR, 13C{1H} NMR, and 1H-1H COSY analyses. Ruthenium(II/III) complexes of this ligand have been prepared, and characterized by elemental analyses, molar conductance measurements, magnetic susceptibility, FT-IR, FAB-Mass, NMR, and electronic spectral studies. There are two different formulations: [Na]?[cis,cis-RuCl2(DMSO-S)2 (OFAD)]-, and [X]?[mer-RuCl3(DMSO-S)(OFAD)]- where OFAD = (7E)-9-fluoro-3-methyl-10-(4-methyl-piperazin-1-yl)-7-(phenylimino)-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline6-carboxylic acid; and DMSO = dimethylsulfoxide and [X]?=[H(DMSO)2]? or Na?. All the complexes are found to possess plasma proteins interaction in blood and exhibit prominent antibacterial activity against pathogenic Electronic supplementary material The online version of this article (doi:10.1007/s00044-012-9986-0) contains supplementary material, which is available to authorized users. R. Mehrotra (&) S. N. Shukla P. Gaur Coordination Chemistry Research Lab, Department of Chemistry, Govt. Science College, Jabalpur, MP 482001, India e-mail:
[email protected] S. N. Shukla e-mail:
[email protected] Present Address: R. Mehrotra Department of Engineering Chemistry, ITM University, Gwalior, MP, India
Escherichia coli in comparison to Ofloxacin and Ciprofloxacin. Keywords Escherichia coli Ofloxacin Ruthenium Schiff base Sulfoxide
Introduction Increasing multidrug-resistant pathogens have become a serious problem especially during the last decade. A more controlled usage of these drugs may be a way to partially counterbalance this challenge. However, the design of new agents active against resist organism remains a topic of critical importance (Matsuoka, 2010); (Shafiee et al., 2009). Discovery of fluoroquinolone (FQs) during the 1980s improved the treatment of infectious diseases, because of their fewer toxic side effects. This class of compounds, in comparison with the previous existing bactericidal drugs, has enhanced pharmacokinetics properties and shows extensive potency against various parasites, bacteria, and mycobacteria, including resistant strains (Dealmeida et al., 2007). These compounds were introduced for clinical use in 1982, and are the latest to join chemotherapy of tuberculosis. Ofloxacin, FQs, is known to have significant bactericidal activity against several bacterial strains showing good penetration rate (Grimaldo et al., 2001); (Berning, 2001). In recent years, many countries have been facing high resistance of Escherichia coli to Ofloxacin because of increasing irrational consumption rate, transmission of resistant isolates between people, and consumption of food from animals that have received antibiotics (Alex et al., 2001); (Umolu et al., 2006). The increasing and indiscriminate uses of antibiotics and poor patient compliance have led to development of
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bacterial resistance to antibiotics (Chatterjee et al., 2009). The incidence of microbial drug resistance is alarming and, in view of its development, pharmaceutical industries are shifting away from traditional strategies to newer approaches to cope with this problem (Westby et al., 2005); (Huelsmann et al., 2006); (Jabra-Rizk et al., 2006). The demonstrated antibacterial (Thangadurai and Ihm, 2003); (Thota et al., 2009); (Shukla et al., 2009), antimicrobial (Raman et al., 2008); (Chittilappilly and Yusuff, 2008), antitumor (Serli et al., 2003), and antimetastatic activities (Bergamo et al., 2004); (Velders et al., 2004) of several ruthenium complexes have generated a substantial amount of interest in the synthesis of new ruthenium sulfoxide compounds as potential agent against resist pathogen. Since antimicrobial resistant patterns are constantly evolving, and present global public health problem, there is the necessity for constant antimicrobial sensitivity surveillance. This will help us provide safe and effective empiric therapies. With this view, we have synthesized an Ofloxacin derivative and explored its combination with selected ruthenium sulfoxide precursors anticipating better reactivity in the resulting compounds against E. coli.
Experimental Materials and methods RuCl33H2O (E. Merck), Ofloxacin (Macleod’s pharmaceuticals), Aniline (E. Merck), Muller-Hinton Agar (Himedia), and Sodium dodecylsulphate (SDS) (E. Merck) were used as received. Analytical grade Dimethylsulfoxide (E. Merck), and routine solvents were used without further purification for synthetic purposes. Citrate buffers were prepared by mixing of citric acid and sodium monohydrogentetraphosphate. Blood plasma samples were separated from human pool whole blood. Electronic absorption spectra were recorded using shimadzu-1700 UV–Vis spectrophotometer equipped with a PC. Conductivity measurements were carried out at 25°C on an EI-181 conductivity bridge with a dipping type cell. FT-IR spectra were recorded in KBr pellets on shimadzu-8400 PC, FT-IR spectrophotometer. 1H-NMR, 13 C{1H}NMR, and COSY-NMR spectra were recorded in acetone-d6 on a Bruker DRX-300 NMR spectrometer. The chemical shifts were expressed as d (ppm) from internal reference standard TMS. Gouy‘s method was employed for measurement of magnetic susceptibility. Hg[Co(NCS)4] was used as standard. Diamagnetic correction was made by using Pascal’s constant. Elemental analyses (CHN) were performed on Elementra Vario EL III, Elemental analyzer. FAB-Mass spectra were recorded on Jeol SX-102 Mass spectrometer.
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Preparation of Schiff base ligand Synthesis of (7E)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-(phenylimino)-2,3-dihydro-7H[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid, (OFAD) To the solution of Ofloxacin (0.10 g, 0.277 mmol) in glacial acetic acid (2 ml), a mixture of aniline (0.025 ml, 0.277 mmol) in ethanol (20 ml) was added and kept under reflux for 20 h. Color of reaction solution changes from colorless to brown red. The volume of reaction mixture was then reduced by rotary evaporation. The solids obtained were filtered under vacuum, washed with cold ethanol, and dried under vacuum over fused CaCl2. Purity of product was assured by TLC. Yield: 0.1082 g (89.6%); Mp [ 220°C. IR: (KBr, cm-1) 3250(w), m(–OHcarboxylic); 1711(s), m(C=Ocarboxylic); 1598(s), m(C=N); 1230(s), m(C– F); 1058(s), m(C–O–C). 1H-NMR (acetone-d6): 11.14(brs, 1H, COOH); 8.64(s, 1H, H5); 7.43(t, 2H, Ar-Hmeta); 7.01(t, 1H, Ar–Hpara); 6.86(d, 2H, Ar–Hortho); 6.52(m, 1H, Ar–H8); 4.39–4.84(m, 10H, CH2); 2.38(m, 1H, CH); 2.18(s, 3H, N–CH3); 1.62(d, 3H, CH3). 13C{1H}NMR (acetone-d6): 166.3(COOH); 164.6(C=N); 144.8(C–F); 153.2–99.6(Ar–C); 68.2(O–CH2); 54.5(CH); 54.8, 50.3(CH2); 44.4(N–CH3); 18.2(CH3). Electronic spectra (kmax, nm (e in M-1 cm-1)) in acetonitrile: 308(763), 272(866). Anal. Calc. for C24H25N4O3F (Ms = 436): C, 66.04; H, 5.77; N, 12.83. Found: C, 65.18; H, 5.72; N, 12.72. FAB-MS [M ? H]? m/z = 437. Preparation of complexes Synthesis of [Na]?[cis,cis-RuCl2(DMSO-S)2(OFAD)]-: complex (1) The precursor complex, [cis,fac-RuCl2(DMSO-S)3(DMSOO)] (1a), was prepared according to the procedure cited in the literature (Evans et al., 1973). The Schiff base ligand OFAD (0.09 g, 0.207 mmol) dissolved in acetone (10 ml) was then added to a solution of recrystallized [cis,facRuCl2(DMSO-S)3(DMSO-O)] (0.10 g, 0.207 mmol), in DMSO (0.5 ml). Reaction mixture was kept under reflux for 4 h. Color of reaction solution changes from yellow to deep red. Volume of reaction solution was reduced under vacuum. Immediately after addition of sodium chloride (0.0120 g, 0.207 mmol) solution, a precipitate formed. The reaction mixture remained under stirring at room temperature for 2 h. The red solid obtained was filtered, washed with acetone/diethyl ether, (1:1) solvent mixture, and then vacuum dried. Yield: 0.1428 g (87.9%); Mp [ 220°C. IR: (KBr, cm-1) 1628(s), mas(COO-); 1582(s), m(C=N); 1396(s), ms(COO-); 1226(s), m(C–F); 1106(s), m(SO); 1057(s), m(C–O–C); 554(s), m(Ru–O); 402(m), m(Ru–S);
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339(s), 332(sh), m(Ru–Cl); 281(s), m(Ru–N). 1H-NMR (acetone-d6): 8.82(s, 1H, H5); 7.56–6.58(m, 6H, Ar–H); 4.96–4.46(m, 10H, CH2); 3.64(s, 6H, S–CH3); 3.46(S, 6H, S–CH3); 2.35(m, 1H, CH); 2.14(s, 3H, N–CH3); 1.67(d, 3H, CH3). 13C{1H}NMR (acetone-d6): 166.9(COOH); 169.2(C=N); 144.7(C–F); 155.6–103.2(Ar–C); 68.6(O– CH2); 54.2(CH); 54.9, 50.7(CH2); 45.9, 45.3(S–CH3); 44.8(N–CH3); 18.2(CH3). Electronic spectra (kmax, nm (e in M-1 cm-1)) in acetonitrile: 682(83), 536(109), 413(481), 342(832), 301(964). Dm at 25°C (X-1 in M-1 cm-1): 118 in DMSO. Anal. Calc. for C28H36N4S2O5 FCl2NaRu (Ms = 786): C, 42.75; H, 4.61; N, 7.12; S, 8.15. Found: C, 42.68; H, 4.67; N, 7.08; S, 8.22. FAB-MS [M ? Na]? m/z = 809. Synthesis of [H(DMSO)2]?[mer-RuCl3(DMSOS)(OFAD)]-: complex (2) The precursor complex, [(DMSO)2H]?[trans-RuCl4(DMSOS)2]- (2a), was prepared according to the procedure proposed by Alessio et al. 1991. The Schiff base ligand OFAD (0.0784 g, 0.18 mmol) dissolved in acetone (9 ml) was added to the solution of recrystallized [(DMSO)2H]?[transRuCl4(DMSO-S)2]- (0.10 g, 0.18 mmol) in DMSO (0.4 ml) in a two-necked flask. Reaction mixture was kept under reflux for 3 h, in an inert atmosphere. Color of reaction solution changed from red orange to light orange. Volume of reaction mixture was reduced under vacuum by rotary evaporation. The yellow orange solid obtained was filtered, washed several times with acetone/diethyl ether, (1:1) solvent mixture, and then dried. Yield: 0.1264 g (80.1%); Mp [ 220°C. IR: (KBr, cm-1) 1635(s), mas(COO-); 1586(s), m(C=N); 1384(s), ms(COO-); 1232(s), m(C–F); 1096(s), 1054(s), m(SO); 1062(s), m(C–O–C); 724(brs), m[(DMSO)2H]?; 550(s), m(Ru–O); 403(m), m(Ru–S); 331(s), 328(sh), m(Ru–Cl); 273(s), m(Ru–N). Electronic spectra (kmax, nm (e in M-1 cm-1)) in acetonitrile: 483(114), 399(502), 338(645), 297(841). leff = 1.84 lB. Dm at 25°C (X-1 in M-1 cm-1): 110 in DMSO. Anal. Calc. for C30H43N4S3O6FCl3Ru (Ms = 878): C, 41.02; H, 4.93; N, 6.38; S, 10.95. Found: C, 40.94; H, 4.88; N, 6.30; S, 10.88. FAB-MS [M ? H]? m/z = 879. Synthesis of [Na]?[mer-RuCl3(DMSO-S)(OFAD)]-: complex (3) The precursor complex, (Na)?[trans-RuCl4(DMSO-S)2](3a), was prepared according to the procedure given in the literature (Alessio et al., 1991). The Schiff base ligand OFAD (0.1031 g, 0.237 mmol) dissolved in acetone (11 ml) was added to a solution of recrystallized (Na)? [transRuCl4(DMSO-S)2]-, (0.10 g, 0.237 mmol), in DMSO (0.4 ml). Reaction mixture was kept under reflux for 2 h, in an
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inert atmosphere. Color of reaction solution changed from orange to yellow orange. The volume of yellowish orange transparent solution was then reduced by vacuum evaporation. The solid obtained was filtered, washed with acetone/diethyl ether, (1:1) solvent mixture, and then dried. Yield: 0.1344 g (76.4%); Mp [ 220°C. IR: (KBr, cm-1) 1626(s), mas(COO-); 1590(s), m(C=N); 1392(s), ms(COO-); 1231(s), m(C–F); 1108(s), m(SO); 1056(s), m(C–O–C); 552(s), m(Ru–O); 400(m), m(Ru–S); 338(s), m(Ru–Cl); 277(s), m(Ru–N). Electronic spectra (kmax, nm (e in M-1 cm-1)) in acetonitrile: 475(108), 402(511), 341(879), 300(963). leff = 1.79 lB. Dm at 25°C (X-1 in M-1 cm-1): 123 in DMSO. Anal. Calc. for C26H30N4SO4FCl3NaRu (Ms = 744): C, 41.97; H, 4.06; N, 7.53; S, 4.31. Found: C, 42.01; H, 4.08; N, 7.46; S, 4.39. FABMS [M ? Na]? m/z = 767. Results and discussion The complexes 1–3 were obtained by the reaction between an Ofloxacin Schiff base ligand and the selected ruthenium(II/III) sulfoxide precursor in acetone. The desired product is formed as solids on vacuum evaporation. Empirical formula of synthesized ligand and complexes 1–3 were in good agreement with elemental analyses. Reactions involved in the formation of complexes 1–3 are well-known substitution reactions. Molecular weights were determined by FAB-Mass, where pseudo-molecular ion peak had appeared. The higher values of molar conductance in DMSO for complexes 1–3 were indicative of their ionic nature (Shukla et al., 2009); (Alessio et al., 1991). Infrared spectral analysis In FT-IR spectra of Schiff base ligand, the complete absence of a peak at 1,621 cm-1 due to –C=O group of Ofloxacin has indicated the complete condensation of the carbonyl group, and the appearance of a new absorption band at 1,598 cm-1 is attributable to the characteristic stretching frequencies of imino linkage m(C=N). In complexes, this band was shifted to 1,590–1,582 cm-1, because of the coordination of imino nitrogen to the ruthenium center (Chandra et al., 2009). This view was also confirmed by the appearance of m(Ru–N) stretching band observed at *280 cm-1. The band observed at *1,058 cm-1 corresponding to C–O–C stretching of ether group (Okeri and Arhewoh, 2008) is found almost at the same position both in ligand and complexes, as that was observed in Ofloxacin indicating the non-involvement of the oxygen atom of C–O–C in coordination with metal ion. Two characteristic absorption bands at around 1,600 and 1,400 cm-1 were observed because of the asymmetric and symmetric modes of m(COO-), respectively. The carboxylate
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group can bind to metal ions in a monodentate, bidentate, or bridging manner (Nakamoto 1992). The frequency difference [Dm = mas(COO-) - ms(COO-)] can be used as an indication of binding mode of the carboxylate ion. If Dm [ 200, this group is probably bound in a monodentate fashion (Deacon and Phillips, 1980), as it was observed for the complexes 1–3 reported herein. The appearance of m(Ru–O) band (Shukla et al., 2009), near 550 cm-1, also confirms our view. In complex 1, the disappearance of the band in the region of 915 cm-1, due to m(DMSO-O) (Evans et al., 1973), indicated its substitution with ligand. However, in 1–3, one or two bands were observed between 1,096 and 1,108 cm-1 because of m(DMSO-S). The absorption bands for m(Ru–S) and m(Ru–Cl) modes were observed near 400 and 330 cm-1, respectively. In complex 2 a, a broad band appeared at 724 cm-1 along with a sharp band at 1,054 cm-1 assigned for free DMSO, indicating the presence of hydrogen-bonded DMSO (Shukla et al., 2009); (Alessio et al., 1991); (Alessio et al., 1988). Fig. 1
1
H-1H COSY spectrum of Schiff base ligand
Electronic spectral analysis and magnetic moment In electronic spectra of ligand, two bands appearing in UV region, at 272 and 308 nm were attributed to p ? p* and n ? p* transitions, respectively. Shifting of these bands in complexes with color change authenticate the coordination of metal ion with ligand. Complex 1 was diamagnetic (low spin d6, S = 0), as expected for low spin Ru(II) complexes. Five bands were observed in electronic spectra. The two weak absorption bands observed in the visible region at 682 and 536 nm were due to d–d transitions, namely, 1A1g ? 1T1g and 1 A1g ? 1T2g, respectively. Higher energy absorption at 413 nm was probably due to MLCT transition. However, other higher energy absorption bands in the region below 340 nm were attributed to p ? p* intraligand transition, occurring in coordinated p-acidic imine ligand (Bora and Singh, 1978); (Sarma and Poddar, 1988); (Lever, 1984); (Dutta and Bhattacharya, 2003). Complexes 2 and 3 were paramagnetic with magnetic moments of 1.84 and 1.79 BM, respectively, as expected for low spin (d5) Ru(III) complexes. Four bands appeared in between 483–475, 402–399, 341–338, and 300–297 nm. Electronic spectral assignment suggested octahedral environment around ruthenium center. NMR spectral studies 2D NMR spectrum In 1H-1H COSY spectrum of Schiff base ligand (Fig. 1), cross peaks were observed because of the proton–proton coupling between connective carbon atoms (Shukla et al.,
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2009). The signal that appears at d2.38 ppm for CH is connected by cross peaks to the two separate signals appearing at d1.62 ppm for CH3 and at d4.84 ppm for CH2 (Mohammadi et al., 2008), and the signal for aromatic proton appearing at d7.43 ppm for Hmeta is connected to the signals that are observed at d7.01 ppm for Hpara and d6.86 ppm for Hortho by cross peaks. 1
H-NMR spectrum
In the spectra of free ligand, the downfield signal at d11.14 ppm assigned for carboxylic proton (Raamnb et al., 2002) is found disappear in Ru(II) complex indicating the deprotonation of –COOH group and involvement of carboxylate oxygen in complexation. In complex 1, two signals were observed with intensity of 1:1 indicating two possible environments for sulfoxide protons. The singlet appearing at d3.64 ppm was assigned for six DMSO protons trans to Cl and at d3.46 ppm trans to Schiff base ligand (Shukla et al., 2009); (Alessio, 2004). 13
C{1H}NMR spectrum
In the spectra of free ligand, the signal for –C=N carbon appearing at d164.6 ppm shows downfield shifts in Ru(II) complex to d169.2 ppm indicating involvement of –C=N nitrogen in coordination with metal ion (Chandra et al., 2009). In complex 1, signals for (S–C) carbon were observed at d45.9 and d45.3 ppm (Alessio et al., 1988); (Alessio, 2004). The signals observed in NMR spectra of complexes 2 and 3 were too broad, due to paramagnetic ion, but on the
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basis of UV–Vis spectra and FT-IR spectra, it was evident that probably one Cl is replaced (Srivastava and Fronczek 2005), along with H? ion of –COOH group.This was also verified qualitatively by silver nitrate test. Thus, the binding modes of Schiff base ligand with ruthenium(II/III) are concluded on the basis of above discussion and the results of the analyses above obtained. We have proposed the structure for Schiff base ligand and the complexes 1–3 (Fig. 2).
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then incubated at 37 ± 1°C for 24–48 h in a refrigerated incubator. Results were obtained in the form of inhibition zone, which were measured in mm. All the three complexes 1–3 are more active in comparison with Schiff base ligand and Ofloxacin, probably because of the enhanced lipophilicity of complexes, which leads to the breakdown of permeability barrier of cell and the blocking of the binding sites in enzyme of micro organisms, thus retarding normal cell process in bacteria and affecting their growth (Priya et al., 2009); (Raman et al., 2008).
Antibacterial screening Minimum inhibitory concentration (MIC) The complexes 1–3, their precursor’s 1a–3a, and Schiff base ligand (OFAD) were screened for antibacterial properties against gram-negative bacteria E. coli, MTCC 1304. Muller-Hinton agar plates (MHA) were prepared, and 50 ll suspension of E. coli containing approximately 105 CFU (Colony Forming Unit) was applied to plate by spreading with the help of swap or spreader (Raman and Raja, 2007); (Pelczar et al., 2001). The deep well was made on plates, which was then filled with 50 ll of sample solution. The 0.2 lg/ml solution mixture of Ofloxacin and Ciprofloxacin was used for comparison. These plates were
The MIC test is used to establish the biostatic activity and spectrum of action, for complexes 1–3, according to the resistances of the studied microorganisms. It was determined by the classic method of successive dilution (Mazzola et al., 2009). In 12 screw tubes designated, A–L (10 9 100 mm), 1 ml of Muller-Hinton broth mediums was distributed in each tube, except for the tube A. All the tubes were placed at autoclave for sterilization. In tubes A and B, 1 ml of test solution, with a concentration of 9.5 lg/ml (complexes
Fig. 2 Structure of Schiff base ligand and complexes 1–3
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1–3/Schiff base ligand) was added; tube B was stirred and 1 ml mixture of it was taken out and transferred to tube C. This successive transference was repeated until tube K. Incubation at 37 ± 1°C temperature was developed for 24–48 h (Fig. 3). MIC is the concentration of the higher dilution tube in which the bacterial growth was absent, and the results are presented in Table 1. Complex 3 was the most active to inhibit bacterial growth at 0.3 lg/ml.
Table 1 Antibacterial screening against Escherichia coli
3a
20 ± 1.63
–
Compounds
*Diameter of inhibition zone (in mm.) ± SEM
MIC (lg/ml)
OFAD
22 ± 0.82
0.2
1
25 ± 0.47
0.5
1a 2
07 ± 0.82 26 ± 1.63
– 0.3
2a
19 ± 1.70
–
Spectrophotometric determination of synthesized complexes in blood plasma
3
28 ± 1.70
0.3
Ciprofloxacin
21 ± 0.92
–
Medicinal chemistry is predominately focused on design of organic molecules, whereas the incorporation of inorganic components into drugs is less investigated. Since the function of metal drugs is highly influenced by plasma proteins; therefore we have decided to examine the plasma protein–drug interactions for complexes 1–3. The 0.1% solution of complexes were prepared and optimized by standard procedure reported by Ciric et al., 2007. Blood plasma sample (1.0 ml) was mixed with different volumes of 0.1% solution of complexes. According to the literature data, FQs in plasma were bounded to plasma proteins. Hence, in order to coagulate proteins and prevent FQs binding with proteins (mainly albumin), sodium dodecylsulphate (SDS) was added. SDS also creates hydrophobic environment. The plasma samples were then centrifuged at 1,500 rpm for 30 min. Supernatant was separated, and, after filtration was transferred into a 5 ml volumetric flask. The flask was filled with citrate buffer (pH = 7.4) to the mark. Electronic spectra of samples were recorded in UV range and compared against plasma blank.
Ofloxacin
22 ± 0.68
–
Fig. 3 Scheme for successive dilution method
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* Mean value of inhibition zone ± Standard error mean (SEM)
Fig. 4 UV spectra of plasma interaction with Schiff base ligand and complex 1 in addition of SDS
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The UV spectrum of samples consist of two major bands (Fig. 4): one higher energy band at about 300 nm due to the p ? p* transition in aromatic ring; and the other at 340 nm due to n ? p* transition. Intensities of these band increase with the concentration of complex and pH (up to 8), which shows a clear hyperchromic shift, confirming that plasma proteins interfere with complexes (Slim et al., 2007).
Conclusion Ruthenium(II/III) ionic complexes have been synthesized by the reaction of Schiff base derivative of Ofloxacin and ruthenium sulfoxide precursor. The coordinated Cl are at cis position in Ru(II) complex, while in Ru(III) compounds, they attain mer configuration. These complexes are novel due to their specific structure and biological activity against E. coli. The antibacterial results (inhibition zone) showed that synthesized compounds have higher potency as compared with ruthenium precursors, ligands, and FQs. Hyperchromic shifts wrap up interaction of complexes with plasma protein in blood. The use of ruthenium medicinal chemistry could be interesting as a potentially less toxic alternative to platinum. The results reported herein indicate that ruthenium complexes show potential antibacterial activity, and their activity against other microorganisms should be investigated to collect more data that could allow the establishment of structure–activity relationships. Therefore, based on the above discussion, it can be easily concluded that the inherent activity of these compounds gives a new look to Metallo-antibiotics. Acknowledgments The authors offer their thanks to the Head, Department of Chemistry, Govt. Science College, Jabalpur for providing laboratory facilities. Thanks are also due to SAIF, CDRI, Lucknow, for the recordings of spectra and elemental data. RM is thankful to the CSIR, New Delhi, India for the sanction (F. No. 08/31(0008)/2009-EMR-I) toward the Senior Research Fellowship.
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