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

Year 2020, , 28 - 33, 12.01.2020

Sanaz Hamidi Enis Fuat Tüfekci , Neslihan Demirbaş , Yasemin Ünver , Ali Osman Kılıç

https://doi.org/10.30934/kusbed.604829

Abstract

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.

Keywords

Chromobacterium violaceum, antibiotic resistance, derivatives, antimicrobial tests

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

Abstract

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.

Keywords

Chromobacterium violaceum, antibiyotik direnci, türevler, antimikrobiyal testler

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