Tiyazol-fenilasetik asit bileşiklerinin dual antibakteriyel-COX enzim inhibitörleri olarak sentezleri

Year 2017, Volume: 42 Issue: 4, 741 - 746, 31.12.2017

Hülya Karaca Gençer

https://doi.org/10.17826/cutf.306424

Cited By: 3

Abstract

Amaç: Bu çalışmanın amacı inflamasyon ve enfeksiyon geçiren hastalara önerilebilecek çift etkili potansiyel ilaçlar sunmak olup bu bağlamda tiyazol fenilasetik asit türevlerinin antienflamatuvar ve antibakteriyal aktiviteleri araştırmaktır.

Gereç ve Yöntem: Yeni sentezlenen bu bileşiklerin antienflamatuvar etkileri fluorometrik yöntem ile belirlenmiştir. Bu yöntem COX1 (siklooksigenaz 1) ve COX2 (siklooksigenaz-2) enzim inhibisyonu sırasında oluşan ara ürünler prostaglandin-1 ve prostaglandin-2’nin belirlenmesine dayanmaktadır. Ibuprofen ve Nimesulid  referans ilaç olarak kullanılmıştır. Antimikrobiyal aktiviteyi belirlemek üzere mikrobroth dilüsyon testi kullanılmıştır. Bileşiklerin iki kat seri dilüsyonları mikroorganizmalara karşı denenmiş ve bileşiklerin minumum inhibisyon konsantrasyonları CLSI’ye göre belirlenmiştir. Kloromfenikol control ilaç olarak kullanılmıştır. 

Bulgular: Fluorometrik yöntem ve antimikrobiyal aktivite sonuçları karşılaştırılmıştır. 2b nin önemli COX1 ve COX2 inhibisyon etkiti olduğu gözlenmiş olup, 4-klorofenil ve fenil grubu taşıyan 2d nin ise aktivitesinin daha iyi olduğu gözlenmiştir. Aynı sırada 2d nin antimikrobiyal etkisinin kontrol ilaç olarak kullanılan kloromfenikole eş ya da daha iyi olduğu belirlenmiştir. 

Sonuç: Sentezlenen bileşikler arasında 2d hem antiinflamatuar hemde antibakteriyal aktivite göstermiştir. 2d umut veren potansiyel bir ilaç olarak değerlendirilebililr. 2d’nin iskelet yapısı üzerine yapılacak olan ileri çalışmalar yeni, alternatif dual antiinflamatuvar ve antibakteriyal ilaç gelişimine ve böylece her iki hastalığın semptomlarından muzdarip hastalar için umut olacaktır. 

Keywords

Inflamasyon, enfeksiyon, siklooksigenaz, antibakteriyal

Synthesis of thiazole-phenylacetic acid compounds as dual antibacterial-COX enzymes inhibitors

Abstract

Purpose: Present a new potential dual drug for patient suffering both inflammation and infection was aim of this study therefore investigation of anti-inflammatory and antimicrobial activity of new thiazole-phenylacetic acid compounds derivatives as a potential dual drug was carried out. 

Materials and Methods: Anti-inflammatory activity of new synthesize drugs were determined via fluorometric assay. Assay based on fluorometric detection of intermediates prostaglandin G1 and G2 during COX1(cyclooxygenases-1) and COX2 (cyclooxygenases-2) enzyme inhibition, respectively. Ibuprofen and Nimesulide were used as reference drugs. Antimicrobial activity of compounds in parallel were evaluated with microbroth dilution assay. Two-fold serial dilution of compounds were tested against microorganisms and minimum inhibition concentration of compound were determined according to CLSI (Clinical and Laboratory Standards Institute). Chloramphenicol was used as a control drug.  

Results: Fluorometric assay and antimicrobial assay results were compared. The observation was compound 2b had important inhibitory activity on COX1 and COX2 but activity of 2d carrying 4-chlorophenyl and phenyl was more successful than 2b and also antimicrobial activity of 2d against microorganism was better or same as reference drug chloramphenicol. 

Conclusion: Between the new synthesized compound, 2d exhibited remarkable anti-inflammatory and antibacterial activity. 2d can be evaluated as a promising drug potential. Further investigation on scaffold of 2d will help to develop new alternatives for dual anti- inflammatory and antibacterial agent which can provide relief for patients in suffering from the symptoms of these diseases. 

Keywords

Inflammation, infection, cyclooxygenases, antibacterial

References

• 1. Cekici A, Kantarcı A, Hastürk H, Dyke TEV. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Peridontol. 2000. 2014;64:57-60.
• 2. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860-7.
• 3. Amor S, Puentes F, Baker D, Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010;129:154-69.
• 4. Libby P. Inflammation and cardiovascular disease. Am J Clin Nutr. 2006;83:456S-460S.
• 5. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953-64.
• 6. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140:771-6.
• 7. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:986-1000.
• 8. Ong CKS, Lirk P, Tan CH, Seymour RA. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res. 2007;5:19-34.
• 9. Zaghi A, Arfaei S. Selective COX-2 Inhibitors: A review of their structure-activity relationship. Iran J Pharm Res. 2011;10:655-83.
• 10. Claria J. Cyclooxygenase-2 biolog. Curr Pharm Des. 2003;3:2177-90.
• 11. Bekhit AA, Abdel-Azeim T. Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents. Bioorg Med Chem. 2004;12:1935–45.
• 12. Ahmadi F, Ghayahbashi MR, Sharifzadeh M, Alipoiur E, Ostad SN, Vosooghi M, et al.. Synthesis and evaluation of anti-inflammatory and analgesic activities of new 1,2,4-triazole derivatives. Med Chem. 2015;11:69-76.
• 13. Bekhit AA, El-Sayed OA. Aboulmagd E, Park JY. Tetrazolo[1,5-a]quinoline as a potential promising new scaffold for the synthesis of novel anti-inflammatory and antibacterial agents. Eur J Med Chem. 2004;39:249-55.
• 14. Moneer AA, Mohammed KO, El-Nassan HB. Synthesis of novel substituted thiourea and benzimidazole derivatives containing a pyrazolone ring as anti-inflammatory agents. Chem Biol Drug Des. 2016;87:784-93.
• 15. Paramashivappa R, Phani Kumar P, Subba Rao PV, Srinivasa Rao A. Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors. Bioorg Med Chem Lett. 2003;13:657-60.
• 16. Eswaran S, Adhikari AV, Shetty NS. Synthesis and antimicrobial activities of novel quinoline derivatives carrying 1,2,4-triazole moiety. Eur J Med Chem. 2009;44:4637–47.
• 17. Bekhit AA, Ashour HM, Abdel Ghany YS, Bekhit AD, Baraka A. Synthesis and biological evaluation of some thiazolyl and thiadiazole derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Eur J Med Chem. 2008;43:456-63.
• 18. [K548]Cyclooxygenase-1(COX-1) Inhibitor screening kit (Fluorometric) http://www.biovision.com/cyclooxygenase-1-cox-1-inhibitor-screening-kit-fluorometric.html (accessed Feb 2017).
• 19. [K547]Cyclooxygenase-2 (COX-2) Fluorescent Inhibitor Screening Kit (Fluorometric) http://www.biovision.com/cox-2-inhibitor-screening-kit-fluorometric.html (accessed Feb 2017).
• 20. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Ninth Edition. CLSI document M07-A9.