Üç Thiazolidine-4-Karboksilik Asit Türevinin Pseudomonas, Acinetobacter, Staphylococcus Aureus ve Escherichia Coli Bakterilerine Karşı Antibakteriyel Özelliklerinin İncelenmesi

Öz

Çok ilaca dirençli bakterilerin tedavisi, halk sağlığı için artan bir küresel sorundur. Bu dirence ayak uydurabilmek için yeni ilaç aktif maddelerine ihtiyaç duyulmaktadır. Tiazolidin-4-karboksilik asitlerin (TCA) doğal olarak oluşan amino asitlerin çeşitli esas işlevlerini taklit ederek bakteri gelişimini engelleyebildiği bilinmektedir. Bu nedenle, ikisi yeni olan üç TCA türevinin sentezlenmesi amaçlanmış ve antibakteriyel aktiviteleri çok ilaca dirençli (MDR) bakteriler üzerinde araştırılmıştır. Bileşikler (la-c), L-Sistein hidroklorür ve dihidroksibenzaldehit türevlerinden sentezlendi ve çoklu ilaç dirençli bakterilere karşı in vitro aktiviteleri CLSI kriterlerine göre Kirby-Bauer yöntemi ile denendi. 1a-c, mevcut antibiyotiklere kıyasla S. aureus gibi Gram pozitif bakterilere ve Pseudomanas, Acinetobacter ve Escherichia coli gibi Gram negatif bakterilere karşı önemli antibakteriyel etki sergiledi. Burada, ılıman şartlar altında yüksek verimle kolaylıkla sentezlenebilen yeni potansiyel antibakteriyel maddeler bildirilmiştir. Ancak, bu üç bileşiğin daha ileri araştırmalarının ve in-vitro etkinlik testlerinin yapılması gerektiği açıktır.

Anahtar Kelimeler

• Anti-bakteriyel maddeler
• ilaç direnci
• sistein
• tiyazolidin-4-karboksilik asit

Examination of antibacterial properties of three thiazolidine-4-carboxylic acid derivatives against Pseudomonas, Acinetobacter, Staphylococcus aureus, and Escherichia coli

Öz

Treatment of multi-drug resistant bacteria is a growing problem for global public health. We need new drugs to keep up with resistant. It is known that Thiazolidine-4-carboxylic acids (TCA) are able to inhibit bacterial growth by mimicking various essential functions of naturally occurring amino acids. Therefore, we aimed to synthesis three TCA derivatives, two of them are novel, and investigated their antibacterial activities on multi-drug resistant (MDR) bacteria. Compounds (1a-c) were synthesized from L-Cysteine hydrochloride and dihydroxybenzaldehyde derivatives and their in vitro activities against multi-drug resistant bacteria were assayed by the Kirby-Bauer method according to CLSI criteria. 1a-c exhibited significant antibacterial effect against Gram-positive bacteria such as S. aureus and Gram-negative bacteria such as Pseudomanas, Acinetobacter, and Escherichia coli superior to current antibiotics. Here, new potential antibacterial agents, which can be easily synthesized in high yield under mild condition, have been reported. But it is clear that further research and in-vitro activity tests of these three compounds should be performed.

Anahtar Kelimeler

• Anti-bacterial agents
• drug resistance
• cysteine
• thiazolidine-4-carboxylic acid

Kaynakça

1. 1. Sriramurthy V, Barcan GA, Kwon O. Bisphosphine-catalyzed mixed double-Michael reactions: Asymmetric synthesis of oxazolidines, thiazolidines, and pyrrolidines. J Am Chem Soc 2007; 129:12928-12929.
2. 2. Song ZC, Ma GY, Lv PC, Li HQ, Xiao ZP, Zhu HL. Synthesis, structure and structure-activity relationship analysis of 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives as potential antibacterial agents. Eur J Med Chem 2009; 44:3903-3908.
3. 3. Moallem SA, Imenshahidi M, Shahini N, Javan AR, Karimi M, Alibolandi M et al. Synthesis, anti-inflammatory and anti-nociceptive activities and cytotoxic effect of novel thiazolidin-4-ones derivatives as selective cyclooxygenase (COX-2) inhibitors. Iran J of Basic Med Sci 2013; 16:1238-1244.
4. 4. Hutt MP, Antibacterial thiazolidine or thiomorpholine substituted quinolones. US Patent 4,473,568 A, 25 Sep. 1984.
5. 5. Onen-Bayram FE, Durmaz I, Scherman D, Herscovici J, Cetin-Atalay R, A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells. Bioorg Med Chem 2012; 20:5094-5102. 6. Li W, Lu Y, Wang Z, Dalton JT, Miller DD, Synthesis and antiproliferative activity of thiazolidine analogs for melanoma. Bioorg Med Chem Lett 2007; 17:4113-4117. 7. Aiello F, Brizzi A, De Grazia O, Garofalo A, Grande F, Sinicropi, MS et al. An approach to the stereo-controlled synthesis of polycyclic derivatives of l-4-thiazolidinecarboxylic acid active against HIV-1 integrase. Eur J Med Chem 2006; 41:914-917.
6. 8. Ha YM, Park YJ, Lee JY, Park D, Choi YJ, Lee EK et al. Design, synthesis and biological evaluation of 2-(substituted phenyl) thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors. Biochimie 2012; 94:533-540.
7. 9. Unger L, DeMoss RD. Action of a proline analogue, l-thiazolidine-4-carboxylic acid, in Escherichia coli. J Bacteriol 1966; 91:1556–1563.
8. 10. Anderson RJ, Groundwater PW, Todd A, Worsley AJ. Antibacterial Agents: Chemistry, Mode of Action, Mechanisms of Resistance and Clinical Applications, John Wiley and Sons; 2012.

9. 11. Wise R, Hart T, Cars O, Streulens M, Helmuth R, Huovinen P, Sprenger M. Antimicrobial resistance. Is a major threat to public health. BMJ 1998; 317:609-610.
10. 12. Chauhan R, Abraham J. In vitro antimicrobial potential of the lichen Parmotrema sp. extracts against various pathogens. Iran J of Basic Med Sci 2013; 16: 882-885.
11. 13. Flaherty JP, Weinstein RA. Nosocomial Infection Caused by Antibiotic-Resistant Organisms in the Intensive-Care Unit. Infect Control Hosp Epidemiol 1996; 17:236-248.
12. 14. Guclu E. Genc H, Zengin M, Karabay O. Effectiveness of menthol and folium menthae piperitae against Acinetobacter baumannii. Afr J Microbiol. Res 2013; 7: 2870-2874.
13. 15. Guclu E, Genc H, Zengin M, Karabay O. Antibacterial Activity of Lythrum salicaria against Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Annu Res Rev Biol 2014; 4:1099-1105.
14. 16. Ogutlu A, Genc H, Dursun T, Zengin M, Karabay O. A new antiseptic - furfurylamine biguanidine derivative synthesis and its effect on multi-drug resistant Acinetobacter baumannii strains. Acta Medica Mediterranea 2014; 30: 133-136.
15. 17. Genç H, Karabay O. The antibacterial activity of 2-aminoindanbiguanide chloride and acetate salts against resistant gram-negative bacilli. Annual Research & Review in Biology 2014; 4:1353-1360.
16. 18. Khan KM, Ullah Z, Lodhi MA, Ali M, Choudhary MI, Rahman A et al. Successful computer guided planned synthesis of (4R)-thiazolidine carboxylic acid and its 2-substituted analogues as urease inhibitors. Molecular Diversity 2006; 10:223-231.
17. 19. Han YK, Park YJ, Ha YM, Park D, Lee JY, Lee N et al. Characterization of a novel tyrosinase inhibitor, (2RS,4R)-2-(2,4-dihydroxyphenyl)thiazolidine-4-carboxylic acid (MHY384). Biochim Biophys Acta 2012; 20:542-549.
18. 20. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard- Eighth Edition. CLSI document M07- A8. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, 2009.
19. 21. Schubert MP. Compounds of thiol acids with aldehydes. J Biol Chem 1936; 114:341-350.
20. 22. Ratner S, Clarke HT, The action of formaldehyde upon cysteine. J Am Chem Soc 1937; 59:200-209.
21. 23. Prabhakar YS, Solomon VR, Gupta MK, Katti SB. QSAR studies on thiazolidines: a biologically privileged scaffold. Top Heterocycl Chem 2006; 4: 161-249. 24. Hahn FE. Thiazolidine-4-carboxylic acid, a selective drug against human cancers. Naturwissenschaften 1980; 67: 307-307.
22. 25. Yang DP, Ji HF, Tang GY, Ren W, Zhang HY. How many drugs are catecholics. Molecules 2007; 12:878-884.
23. 26. Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006; 5:993-996.
24. 27. Dalluge JJ, Nelson BC. Determination of tea catechins. J Chromatogr A 2000; 881:411-424.
25. 28. Ross AB, Kamal-Eldin A, Aman P. Dietary Alkylresorcinols: Absorption, Bioactivities, and Possible Use as Biomarkers of Whole-grain Wheat–and Rye–rich Foods. Nutr Rev 2004; 62:81-95.
26. 29. Kozubek A, Tyman JH. Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles and their biological activity. Chem Rev 1999; 99:1-26.
27. 30. Sanchez PC, Garrido AR, Gallego GG. Lopez, S. V.; Puerto, L. R. M. Methods of use for 2,5-dihydroxybenzene sulfonic acid compounds for the treatment of cancer, rosacea and psoriasis. US Patent 0 149 618 A1, 2007.