Brazilian Medicinal Plant Extracts with Antimicrobial Action Against Microorganisms that Cause Foodborne Diseases
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Studies have shown the significant action of flavonoids as topoisomerase inhibitors, contributing to their antimicrobial activity. According to Plaper et al. (2003), DNA gyrase is defined as an essential enzyme so that DNA replication can be performed, being exclusive to prokaryotes, and an attractive target for drugs with antimicrobial action. Quercetin, apigenin and sakuranet are flavonoids capable of inhibiting Helicobacter pylori 3-hydroxyacyl ACP dehydrase (Zhang et al. 2008). Eleven flavanones with different configurations of hydroxyl groups were evaluated to verify the antimicrobial activity on E. faecalis (Jeong et al. 2009) and many were shown to be efficient, mainly being naringenin and taxifolin. Mori et al. (1987) reported that some flavonoids can affect the DNA of microorganisms, and act in the inhibition of bacterial nucleic acid synthesis. They noted that the incubation with epigallocatechin gallate, myricetin and robinetin resulted in the reduction of DNA, RNA and protein synthesis by Proteus vulgaris and S. aureus.
Mechanisms of Anticancer Drugs
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Most antitumour antibiotics have been produced from bacterial and fungal cultures (often Streptomyces species). They affect the function and synthesis of nucleic acids in different ways: Anthracyclines (e.g. doxorubicin, daunorubicin, epirubicin) intercalate with DNA and affect the topoisomerase II enzyme. This DNA gyrase splits the DNA helix and reconnects it to overcome the torsional forces that would interfere with replication. The anthracyclines stabilize the DNA topoisomerase II complex and thus prevent reconnection of the strands.Actinomycin D intercalates between guanine and cytosine base pairs. This interferes with the transcription of DNA at high doses. At low doses DNA-directed RNA synthesis is blocked.Bleomycin consists of a mixture of glycopeptides that cause DNA fragmentation.Mitomycin C inhibits DNA synthesis by cross-linking DNA, acting like an alkylating agent.
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Peter D O Davies, Stephen B Gordon, Geraint Davies in Clinical Tuberculosis, 2014
Ciprofloxacin (CIP), ofloxacin (OFL), levofloxacin (LEVO), the optical S-(–) isomer of the racemic mixture OFL, gatifloxacin (GATI) and MOXI are the most active fluoroquinolones against M. tuberculosis [4,140–142]. Because LEVO is an isomer of OFL, LEVO will be listed primarily throughout this section. The fluoroquinolones inhibit DNA gyrase [143,144]. They are bactericidal against M. tuberculosis, with MBC/MIC ratios generally between two and four [144,145]. CIP and OFL inhibit M. tuberculosis at concentrations of 0.5–2.0 μg/mL, and LEVO is twice as active as OFL. GATI and MOXI are roughly one doubling dilution more potent in vitro. Point mutations in DNA gyrase lead to resistance, and cross-resistance among these drugs is common [135,143]. A major concern with the use of fluoroquinolones in TB is the rapid development of resistance.
Ozenoxacin: a review of preclinical and clinical efficacy
Published in Expert Review of Anti-infective Therapy, 2019
Jordi Vila, Adelaide A Hebert, Antonio Torrelo, Yuly López, Marta Tato, María García-Castillo, Rafael Cantón
Quinolones act by inhibiting the enzymes DNA gyrase and topoisomerase IV, both of which are involved in bacterial DNA synthesis [28]. DNA gyrase catalyzes the negative supercoiling of DNA, and thus plays an important role in the replication and transcription of DNA, and in organization of the chromosome [29]. The main function of topoisomerase IV is to decatenate the two daughter molecules of DNA after replication [30]. Both enzymes are tetrameric: DNA gyrase consists of two A subunits (GyrA, encoded by the gyrA gene) and two B subunits (GyrB, encoded by the gyrB gene); topoisomerase IV also has two A subunits (ParC or GrlA, the latter in S. aureus, encoded by the parC or grlA genes) and two B subunits (ParE or GrlB, the latter in S. aureus, encoded by the parE or grlB genes) [28]. Some quinolones (e.g. levofloxacin and ciprofloxacin) act preferentially against topoisomerase IV over DNA gyrase [31].
ATP-competitive DNA gyrase and topoisomerase IV inhibitors as antibacterial agents
Published in Expert Opinion on Therapeutic Patents, 2019
Martina Durcik, Tihomir Tomašič, Nace Zidar, Anamarija Zega, Danijel Kikelj, Lucija Peterlin Mašič, Janez Ilaš
The primary role of DNA gyrase is introducing negative supercoils into DNA in advance of the replication fork, while topoisomerase IV is important for chromosome decatenation during DNA replication. DNA gyrase and topoisomerase IV are both active as heterotetrameric structures, such as GyrA2GyrB2 for DNA gyrase, and ParC2ParE2 for topoisomerase IV [3]. The GyrA and ParC subunits contain catalytic tyrosine that covalently binds to DNA through a phosphotyrosyl bond which initiates DNA cleavage. By introducing introduce double-strand breaks into the DNA molecule, and thus release the torsional stress caused by supercoiling is released, with both strands subsequently rejoined [4]. GyrB and ParE contain an ATP-binding site, whereby ATP hydrolysis provides the energy required for the reaction catalysed by GyrA and ParC(GrlA) [5]. The similarities in the structures of DNA gyrase and topoisomerase IV offer an exceptional opportunity for their dual targeting with new antibacterial compounds, to thereby reduce the propensity that the bacteria can develop target-based resistance, as the probability of concurrent mutations on each of these targets will be low [5].
Discovery of N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Wenjie Xue, Yaling Wang, Xu Lian, Xueyao Li, Jing Pang, Johannes Kirchmair, Kebin Wu, Zunsheng Han, Xuefu You, Hongmin Zhang, Jie Xia, Song Wu
Bacterial DNA gyrase B subunit (GyrB) is a promising target for discovery and development of a new class of antibiotics.8 As an indispensable component of DNA gyrase (A2B2), GyrB binds ATP at the ATPase domain and catalyses ATP hydrolysis; it provides energy for DNA supercoiling.9 When the GyrB inhibitor novobiocin was approved for clinical use (cf. Figure 1), antibiotics with the same mode of action were considered as promising therapeutics for the treatment of bacterial infections.7 Since the decline of novobiocin in 1960s due to its toxicity and low efficacy, several diverse GyrB inhibitors have been discovered, e.g. ethyl ureas,10 pyrazolopyridones,11 pyrrolamides,12 and quercetin diacylglycosides.13 Unfortunately, none of these have been approved. Two compounds, i.e. SPR720 (ethyl ureas)14 and DS-2969b (pyrrolamides),15 are in phase I clinical trials (cf. Figure 1), but the clinical outcomes of these chemotypes are also unpredictable. Therefore, the identification of diverse structures as GyrB inhibitors is still necessary.
Related Knowledge Centers
- Apicoplast
- Bacteria
- DNA
- Enzyme
- Helicase
- Plasmodium Falciparum
- Plastid
- Topoisomerase
- Rna Polymerase
- DNA Supercoil