Antibacterial Activity of Novel Derivatives Compounds Containing 1,2,3-Seleniadiazole

Journal of Babylon University/Pure and Applied Sciences/ No.(7)/ Vol.(22): 2014 Antibacterial Activity Of Novel Derivatives Compounds Containing 1,2,3-Seleniadiazole Heterocyclic Ring Against Some Pathogenic Bacteria

Muna sabbar Al-Rubiae , Luma Ali Al- Hilli Department of medical analysis, Babylon Technical Institute [email protected] , [email protected] Nadhir N. A. Jafar , Sadiq J. Baqir Department of Chemistry/ College of Science/ University of Babylon [email protected] , [email protected]

Abstract In the previous study three compounds of semicarbazones (namely, 2: 1-Naphthalen- 1-yl- etylidene-urea, 7a: 1-{4[6-(4-Acetyl-phenoxy)-hexacyloxy]-phenyl}-ethanone Bis, 7b: 1-{4[12-Acetyl- phenoxy)–dodecyloxyl-phenyl}-ethanone Bis) were used to prepare three novel 1,2,3-seleniadiazole heterocyclic ring compounds respectively (namely: (3) :4-naphthalene-1-yl-[1,2,3]selenadiazole, (8a) : 1,6-Bis[4-(1,2,3-seleniadiazol-4-yl) phenoxy] hexane, (8b): 1,12-Bis[4-(1,2,3-seleniadiazol-4-yl) phenoxy] dodecane). We described here the antibacterial activity of semicarbazones compounds and the new series of compounds containing 1,2,3-seleniadiazole heterocyclic ring. The compounds 2, 7a, 7b, 3, 8a, 8b were evaluated in vitro for their antibacterial activity against three genera of Gram negative bacteria; Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and two of Gram positive bacteria, Staphylococcus aureus, S. epidermidis. The novel 1,2,3-seleniadiazole heterocyclic ring compounds (3,8a, 8b) showed very good activity against gram positive bacteria (Staphylococcus aureus, S. epidermidis) and showed moderate antibacterial effect against gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia), whereas the semicarbazones compounds (2, 7a, 7b) had not any effect on all types of bacteria in this study. Key words: semicarbazones , seleniadiazole , the antibacterial activity الخلةصة في دراسة سابقة استخدمت ثلث مركبات من السيميكاربزون (2,7a,7b) لتحضير ثلث مركبات جديدة من -3,2,1 سيلينيادايزول الحاوية على الحلقة الغير المتجانسة (3,8a,8b) على التوالي. وفي هذا البحث درست الفعالية المضادة للبكتريا لكل من مركبات السيميكاربزون و مركبات 3,2,1- سيلينيادايزول. درست الفعالية المضادة للبكتريا لهذة المركبات في المختبر ضد ثلث انواع من البكتريا السالبة لصبغة كرام Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia ونوعين من البكتريا الموجبة لصبغة كرام Staphylococcus aureus, S. epidermidis. مركبات ال 3,2,1- سيلينيادايزول الحاوية على الحلقة الغير المتجانسة (3,8a,8b) اظهرت فعالية جيدة جدا ضد البكتريا الموجبة لصبغة كرام وفعالية متوسطة ضد البكتريا السالبة لصبغة كرام. اما مركبات السيميكاربزون (2,7a,7b) فلم يظهر لها اي تاثير على كل انواع البكتريا تحت الدراسة. الكلمات المفتاحية : السيميكازيزون , سيللينيايزول . النشاط المضاد للبكتريا Introduction Selenium plays an important role as a trace element in living organisms (Birringer et al., 2002). Traces of selenium are important in oxygen metabolism, selenium compounds are considered to be inhibitors of free radicals, as well as anti-inflammatory and antioxidant agents (Zakrzewsk & Krawczyk, 2001). Heterocyclic compounds containing the selenium atom may restrain cancer cell growth (Koketsu et al., 2001). Natural compounds and trace elements, which renew the antioxidative defense system, are emerged as new class of treatment regimen for various diseases including bacterial eradication (Soriano-Garcia, 2004). Selenium containing compounds are of increasing interest because of their chemical properties and have several important biological applications such as bactericidal effect (Abdel-Hafez, 2010), antifungal activity (Zakrzewsk & Krawczyk, 2001), anti-inflammatory activities, immunomodulatory activity (Santhosh, 2010), anti-cancer activity (Soriano-Garcia, 2004) and analgesic activity (Abdel-Hafez, 2008).In this paper, we investigate the antibacterial effect of three novel derivatives compounds containing 1,2,3-

151 Journal of Babylon University/Pure and Applied Sciences/ No.(7)/ Vol.(22): 2014 seleniadiazole heterocyclic ring in vitro and the source of the three compounds (semicarbazones) which are used in preparation of these compounds. Material & Methods Chemical compound Novel derivatives compounds containing 1,2,3-seleniadiazole heterocyclic ring prepared by (Nadhir, 2008) in previous study were used in this research to check there activity against some pathogenic bacteria, and its provide kindly by Nadhir Jafar, College of Science/ University of Babylon. Bacterial strains Three genera of Gram negative bacteria; Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and two of Gram positive bacteria, Staphylococcus aureus, S. epidermidis were used as test organisms in the present study. All strains isolated from clinical specimen in Margan hospital, Babylon, and identified using routine bacteriological methods. Bacterial inoculums The bacterial isolates were grown overnight in nutrient broth (Oxoid) for activation and bacterial suspension were prepared in normal saline at 106 cells/ml following the 0.5 Mcferland tube method (Brown and Poxton, 1996). Inoculation of culture plates Nutrient agar (Oxoid) plates were streaked with microorganisms by swabs, in three different directions on the agar surface (Hindler, 1998). Antibacterial activity assay Disc diffusion method was used to check the antibacterial effect of samples. Discs prepared from Whatman No.3 filter paper of 6 mm diameter were sterilized by autoclaving at 121° C for 15 min. 100 µg of test samples were placed on each disc. The discs were placed on the upper surface of the seeded plate (Parekh et al., 2005). Two types of control viz: solvent discs as negative control and ciprofloxacin 5µg\disc (Himedia) as positive control. The experiment was repeated twice and the mean values were taken. Results and discussion The results of the in vitro antibacterial effect testing of the novel 1,2,3-seleniadiazole heterocyclic ring compounds (3,8a, 8b) showed high activity against gram positive bacteria (Staphylococcus aureus, S. epidermidis) (table 2) and showed moderate antibacterial effect against gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, whereas the semicarbazones (2, 7a, 7b) compounds which were used in preparation of seleniadiazole heterocyclic ring compounds had not any effect on all types of bacteria in this study (table 1). Table (2) Antibacterial activity of 1,2,3-seleniadiazole heterocyclic ring compounds bacterial strains average of inhibition zone diameter (mm) Compound 3 Compound 8a Compound 8b Ciprofloxacin Staphylococcus 16 25 18 27 aureus S. epidermidis 18 23 17 28 Klebsiella 12 13 13 25 pneumonia Escherichia coli 13 14 14 26 Pseudomonas 12 12 13 25 aeruginosa

152 Journal of Babylon University/Pure and Applied Sciences/ No.(7)/ Vol.(22): 2014 Table (1) Antibacterial activity of semicarbazones compounds bacterial strains Average of inhibition zone diameter (mm) Compound 2 Compound Compound 7b Ciprofloxacin 7a Staphylococcus - 9 - 27 aureus S. epidermidis - 8 - 28 Klebsiella - - - 25 pneumonia Escherichia coli - - - 26 Pseudomonas - - - 25 aeruginosa The results obtained in this study indicated that a considerable effect of the novel 1,2,3-seleniadiazole heterocyclic ring compounds as antibacterial substance and these results were in agreement with observations made in previous studies by many researchers on selenium compounds. Abdel-Hafez, (2010) reported that the selenium containing sulfa compounds showed strong bactericidal effect against gram-positive and gram-negative bacteria. Radhakrishna et al. (2010) studied the antibacterial effect of 3-[(phenylcarbonyl)selenyl]propanoic acid an different ester derivatives of 3-[(phenylcarbonyl)selenyl]propanoic acid and benzoylselenoglycolic acid. Their results also showed that the compounds had moderate activity against Staphylococcus aureus, Salmonella typhimurium, Escherichia coli and Bacillus cereus. The results which were obtained from antibacterial activity testing showed that the Gram positive bacteria were more susceptible to 1,2,3-seleniadiazole heterocyclic ring compounds than the Gram negative bacteria. Prakash et al. (2009) reported similar results and showed that the gram positive bacteria were more susceptible to selenium containing compounds. Also Santhosh et al. (2010) studied the antibacterial activity of organoselenium compounds on Helicobacter pylori which is gram negative bacteria and the results showed mild response at 50 and 100 μg/mL. Cell membranes play an important role in sensitivity to antibacterial agents, this may be the reason for sensitivity of Gram positive bacteria to antibacterial agents, single membrane of only peptidoglycan layer in the gram positive bacteria is considerably more accessible to permeation by antimicrobial compounds. By contrast, the Gram negative bacteria have evolved significant permeability barriers it is outer phospholipidic membrane carrying the structural lipopolysaccharide components; the outer membrane is a fairly effective barrier for antimicrobial compounds. (Silhavy et al. 2010) In summary, we have demonstrated the efficient of novel selenium compounds, the novel compound were screened for antibacterial activity and presented good results on inhibition of bacterial growth. The present study indicates that the 3,8a,8b compounds might be useful for developing good antibacterial agents. These compounds need to further studies to determine their side effects in laboratory animals. References Abdel-Hafez, S. H. (2008). Selenium containing heterocycles: Synthesis,anti inflammatory , analgesic and anti-microbial activities of some new4-cyanopyridazine-3 (2H)selenone derivatives. European journal of medicinal chemistry, Vol. 43(9), pp: 1971–1977 Abdel-Hafez, S. H. (2010). Synthesis of novel selenium containing sulfa drugs and their antibacterial activities. Russian journal of bioorganic chemistry. Vol. 36(3), pp: 370-376

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