Bangladesh Journal of Pharmacology Volume: 10; Number 3; Year 2015 Cite this article as: Nastasă C, Duma M, Tiperciuc B, Oniga O. Antimicrobial screening of new 5-(chromene-3-yl) methylene-2,4-thiazolidinediones. Bangladesh J Pharmacol. 2015; 10: 716-17. Antimicrobial screening of new 5-(chromene-3-yl) methylene-2,4-thiazolidinediones Sir, Efforts are being made globally for the control of microbial resistance phenomenon, of its spread, effects, treatment costs and towards finding new effective protocols. One of the main objectives of medicinal chemistry is the design, synthesis and investigation of molecules having value as human therapeutic agents. From the big family of heterocyclic compounds, 1,3- thiazolidine-2,4-diones show a wide spectrum of chemo -therapeutic properties and a considerable amount of work has been done on the synthesis of thiazolidine- dione derivatives as potent antibacterial and antifungal agents (Gouveia et al., 2009, Liu et al., 2011). Chromone and related compounds are wide-spread in nature and exhibit a wide range of pharmacological activity like antibacterial, antifungal (Hatzade et al., 2010, Ali and Ibrahim, 2010), antitumor, anti-oxidant, anti-HIV, antiulcerant, anti-inflammatory. As a continuation of our previous work (Nastasă et al., 2013), the present study shows the antimicrobial screening of a new series of 5-(chromene-3-yl)methy-lene-2,4-thiazolidinediones (Figure 1), for which the chemical synthesis and characterization haven’t yet been revealed. For this purpose, diffusion method was applied (Wayne, 1997), using gentamicin and fluconazole as reference drugs for the antibacterial and antifungal activity, respectively. There were three concentrations of compounds tested: 10, 5 and 1 mg/mL, prepared in dimethylsulfoxide (DMSO). Solvent was used as control and it didn’t display antimicrobial inhibition. Six- millimeter diameter wells were cut from the agar using a sterile cork-borer. After drying for 10-15 min, the six millimeter diameter wells were inoculated with 50 μL from each solution. Plates inoculated with bacteria were incubated for 24 hours and those with fungus 48 hours, at 37ºC. The effects of the new compounds were assessed by measuring the diameter of the growth inhibition zone. All the tests were performed in duplicate and the average was taken as final reading. The antimicrobial effect was evaluated against two Gram-positive (Listeria monocytogenes ATCC 13932 and Staphylococcus aureus ATCC 49444) and two Gram- negative (Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028) bacteriaand one fungal strain, Candida albicans ATCC 10231. The growth inhibitory effects displayed by the 5-(chromene-3-yl) methylene-2,4-thiazolidinedionesare presented in Table I. All compounds displayed moderate to good antimicrobial activity on the selected strains. The most powerful effect was showed against Salmonella typhimurium ATCC 14028, where all molecules, excepting 8, had a very good growth inhibitory activity, even superior to gentamicin, the reference antibacterial drug. The most promising compounds against this Gram negative strain were 2, 3, 7 and 9, for which all concentrations used showed to be very active. The strongest inhibitory effect was displayed by compound 3, at a concentration of 10 mg/mL and compound 4, at a concentration of 5 mg/mL. The second Gram- negative bacterium used in the antimicrobial screening, Escherichia coli ATCC 25922, was less sensitive to the activity of the new synthesized chromenyl-thiazolidine- dione derivatives. Thus, best effect was noted for compounds 9 and 10, at the concentration of 10 mg/ mL, but inferior to that of the antibacterial reference drug. Same substances proved to be the most powerful inhibitors of the growth of Listeria monocytogenes ATCC 13932, their activity being superior to gentamicin. The A Journal of the Bangladesh Pharmacological Society (BDPS) Bangladesh J Pharmacol 2015; 10: 716-717 Journal homepage: www.banglajol.info Abstracted/indexed in Academic Search Complete, Agroforestry Abstracts, Asia Journals Online, Bangladesh Journals Online, Biological Abstracts, BIOSIS Previews, CAB Abstracts, Current Abstracts, Directory of Open Access Journals, EMBASE/Excerpta Medica, Google Scholar, HINARI (WHO), International Pharmaceutical Abstracts, Open J-gate, Science Citation Index Expanded, SCOPUS and Social Sciences Citation Index ISSN: 1991-0088; DOI: 10.3329/bjp.v10i3.24401 Letter to the Editor Figure 1: General structure of 5-(chromene-3-yl)methylene-2,4- thiazolidinediones diameters measured on Staphylococcus aureus ATCC 49444 revealed that compounds were more efficient at 10 mg/mL concentration and that compound 6 was the most active. The compounds showed a moderate activity on Candida albicans ATCC 10231. The most powerful was compound 1, at 10 mg/mL concentration. The less active was compound 8, which displayed a modest antibacterial effect, also. For substances displaying the same R, substitution of chromone with methyl group in position 6 was favorable for the activity against Staphylococcus aureus. Comparing with molecules which have alkyl substi- tutes at the level of thiazolidinedione nitrogen (Nastasă et al., 2013), the introduction of aryl fragment increased the effect against S. aureus bacterial strain. Better growth inhibitory activities expressed by compounds 9 and 10 could be explained by the capacity of amides to form complexes with metals required for microorganism survival. As shown in our previous study, there was not a direct relationship established between the concentration and the effect of the 5-(chromene-3-yl)methylene-2,4- thiazolidinediones. The results obtained may suggest that, for these molecules, the antimicrobial activity is not dose dependent. Cristina Nastasă1, Mihaela Duma2, Brînduşa Tiperciuc1 and Ovidiu Oniga1 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2State Veterinary Laboratory for Animal Health and Food Safety, Cluj-Napoca, Romania. Corresponding author: email: cmoldovan@umfcluj.ro Acknowledgments This paper was published under the frame of European Social Found, Human Resources Development Operational Program 2007-2013, project no. POSDRU/159/1.5/S/136893. References Ali TE, Ibrahim MA. Synthesis and antimicrobial activity of chromone-linked 2-pyridone fused with 1,2,4-triazoles, 1,2,4 -triazines and 1,2,4-triazepines ring systems. J Brazil Chem Soc. 2010; 21: 1007-16. Gouveia FL, de Oliveira RMB, de Oliveira TB, da Silva IM, do Nascimento SC, de Sena KXFR, de Albuquerque JFC. Synthesis, antimicrobial and cytotoxic activities of some 5- arylidene-4-thioxo-thiazolidine-2-ones. Eur J Med Chem. 2009; 44: 2038-43. Hatzade K, Taile V, Gaidhane P, Ingle V. Synthesis, structural determination, and biological activity of new 7-hydroxy-3- pyrazolyl-4H-chromen-4-ones and their o-β-D-glucosides. Turk J Chem. 2010; 34: 241-54. Liu XF, Zheng CJ, Sun LP, Liu XK, Piao HR. Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents. Eur J Med Chem. 2011; 46: 3469-73. Nastasă C, Duma M, Marie C, Scherman D, Tiperciuc B, Oniga O. New N-substituted 5-chromenyl-thiazolidinediones as antimicrobial and antiproliferative agents. Dig J Nanomater Bios. 2013; 8: 1079-87. Wayne PA. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts. NCCLS Approved standard M27-A, USA, 1997. 717 Bangladesh J Pharmacol 2015; 10: 716-717 Table I Diameters of the growth inhibition zones (mm) for the new 5-chromenyl-thiazolidinediones Cp (10/5/1 mg/mL) Gram-positive bacteria (mm) Fungus (mm) Gram-negative bacteria (mm) L. monocytogenes S. aureus E. coli S. typhi C. albicans 1 18/10/12 20/12/12 16/18/18 20/20/18 24/16/16 2 14/14/14 18/12/12 18/18/18 20/20/22 16/16/16 3 16/8/8 20/12/10 14/14/14 24/20/20 22/18/16 4 18/16/16 16/12/12 14/14/14 18/24/20 20/16/16 5 14/16/14 12/14/12 16/16/16 22/18/18 20/18/12 6 16/16/16 28/14/10 18/16/16 18/20/18 22/18/16 7 18/8/10 22/10/10 16/18/18 20/20/20 20/18/18 8 16/16/18 10/12/12 18/18/16 18/18/18 14/14/14 9 20/18/20 20/14/14 20/16/16 22/20/20 20/18/18 10 26/14/14 26/14/12 20/18/16 22/18/18 22/16/14 Gentamicin 18 19 22 18 NT Fluconazole NT NT NT NT 28 mailto:cmoldovan@umfcluj.ro