INVESTIGATION OF ANTIMICROBIAL AND ANTI-QUORUM SENSING PROPERTIES OF SOME DERIVATIVES OF CEPHALOSPORANIC ACID, CIPROFLOXACIN, NORFLOXACIN, AND PENICILLANIC ACID

Öz

Objective: The rapid increase of antibiotic resistance among bacteria is a serious public health problem. Studies have focused on the discovery of new antibiotic molecules and the development of new therapeutic strategies to combat these resistant bacteria. Once it was known that pathogenic bacteria regulate synthesis of virulence factors by the quorum sensing (QS) mechanism, QS inhibition became an attractive target for antibacterial treatment. This study aimed to investigate the antimicrobial activities and anti-QS properties of 16 derivatives of cephalosporanic acid, ciprofloxacin, norfloxacin, and penicillanic acid.

Methods: Antimicrobial activity of the derivatives was tested by the agar well diffusion method against various microorganisms. The minimum inhibitory concentration (MIC) of effective derivatives was assessed by the broth microdilution method. Anti-QS properties were investigated using the soft agar method, observing inhibition of violacein production in Chromobacterium violaceum. The data were compared statistically.

Results: Six norfloxacin derivatives displayed antimicrobial activity against a number of organisms, three of which were more effective than control antibiotics (p<0.05) against some organisms. One ciprofloxacin derivative demonstrated antimicrobial activity against all tested bacteria and was more effective against some bacteria than control antibiotic (p<0.05).  The MIC values of these six norfloxacin and one ciprofloxacin derivatives were between 0.04–6.25 µg/mL and 0.04–3.12 µg/mL, respectively. A cephalosporanic acid and a penicillanic acid derivative displayed anti-QS properties.

Conclusion: This study shows that some new derivatives of cephalosporanic acid, ciprofloxacin, norfloxacin, and penicillanic acid may have potential for development of new antibacterial and anti-QS agents.

Anahtar Kelimeler

• Chromobacterium violaceum
• antibiotic resistance
• derivatives
• antimicrobial tests

BAZI SEFALOSPORANİK ASİT, SİPROFLOKSASİN, NORFLOKSASİN VE PENİCİLLANİK ASİT TÜREVLERİNİN ANTİMİKROBİYAL VE ANTI-QUORUM SENSING ÖZELLİKLERİNİN ARAŞTIRILMASI

Öz

Amaç: Bakteriler arasında antibiyotik direncinin hızla artışı halk sağlığı açısından ciddi bir problem oluşturmaktadır. Çalışmalar, yeni antimikrobiyal moleküllerin keşfi ve dirençli bakterilerle mücadelede yeni tedavi stratejilerinin geliştirilmesi üzerine yoğunlaşmıştır. Patojenik bakterilerin, quorum sensing (QS) mekanizmasını kullanarak virülans faktörlerinin sentezini düzenlediği bulunduktan sonra, QS inhibisyonu antibakteriyel tedavi için cazip bir hedef haline gelmiştir. Bu çalışmada sefalosporanik asit, siprofloksasin, norfloksasin ve penisillanik asit türevi 16 maddenin antimikrobiyal aktivitelerinin ve anti-QS özelliklerinin araştırılması amaçlandı.

Yöntem: Maddelerin antimikrobiyal aktiviteleri çeşitli mikroorganizmalara karşı agar kuyucuk diffüzyon yöntemi ile test edildi. Etki gösteren maddelerin minimum inhibisyon konsantrasyon (MİK) değerleri sıvı mikrodilüsyon yöntemi ile belirlendi. Maddelerin anti-QS özellikleri Chromobacterium violaceum raportör suşunda viyolasin inhibisyonu üzerine yarı-katı agar yöntemi ile araştırıldı. Veriler istatistiksel olarak karşılaştırıldı.

Bulgular: Altı norfloksasin türevi test edilen bakterilerin bir kısmına karşı antimikrobiyal aktivite göstermiş olup üç türevin bazı organizmalara karşı kontrol antibiyotiklerden daha etkili olduğu tespit edildi (p<0,05). Bir siprofloksasin türevi, test edilen tüm bakterilere karşı antimikrobiyal aktiviteye sahip olup bakterilerin bir kısmına karşı kontrol antibiyotiğinden daha etkili olduğu belirlendi (p<0,05). Altı norfloksasin ve bir siprofloksasin türevinin MİK değerleri, sırasıyla 0,04–6,25 µg/mL ve 0,04–3,12 µg/mL aralığında tespit edildi. Bir sefalosporanik asit ve bir penisillanik asit türevinin anti-QS özellik gösterdiği belirlendi.

Sonuç: Bu sonuçlar, bazı yeni sefalosporanik asit, siprofloksasin, norfloksasin ve penicillanik asit türevlerinin yeni antibakteriyel ve anti-QS ajanların geliştirilmesinde potansiyel moleküller olabileceğini göstermiştir.

Anahtar Kelimeler

• Chromobacterium violaceum
• antibiyotik direnci
• türevler
• antimikrobiyal testler

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