6.1.1 Kaempferol and PMFs

Kaempferol show the strongest antibacterial activity (MIC50 = 25 μg/ml) against E. coli DNA gyrase. It inhibits the activity of gyrase enzyme that holds the key role in DNA supercoiling and bacterial growth.

#### Structure of Polymethoxylated flavones

Polymethoxylated flavones (shown in structure) usually found in citrus peel possess broad spectrum antimicrobial activity. It shows antibacterial activity against E. coli and S. aureus with IC50 values ranging from 1.45 to 1.89 mg/ml [8] (see Table 3 for MIC values).

#### 6.1.2 Quercetin

antibacterial agent that impedes the synthesis of nucleic acid may be misinterpreted

The schematic layout demonstrating the natural antioxidant role as antibacterial: (a) representing inhibition of energy metabolism; (b) representing disruption of membranes; and (c) representing interruption in nucleic acid

The mechanisms of action of antioxidants as an antibacterial are shown in

Among the classes of antioxidants, flavonoids significantly show inhibitory activity against nucleic acid synthesis. Interaction of flavonoids with DNA- or with ATP-binding site of gyrase finally leads to the inhibition of nucleic acid synthesis as shown in Figure 2. Metabolism of DNA in bacteria comprises transcription, recombination, DNA replication, and transport of genetic information. A vital enzyme to control vigorous changes of nucleic acid is DNA gyrase. Gyrases, characteristic and crucial bacterial enzymes that change the topology of DNA, are the amiable aim to hit for the antibacterial agents. DNA gyrase, in a reaction that depends on ATP,

The following mechanisms of actions are attributed to the antibacterial action of

as the agent that alters the cytoplasmic membrane functions [7].

flavonoids as reported by different groups of researchers:

a. Alteration of cytoplasmic membrane fluidity

• Impairment of membrane functions

b. Inhibition of cell wall formation

• Interruption of synthesis of nucleic acid

• Inhibition of respiratory metabolism

6.1 Inhibition of nucleic acid synthesis

Figure 2.

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Figure 2.

Antioxidants

synthesis.

c. Inhibition of cell membrane formation

Quercetin is one of the ubiquitous flavonoids, impedes the DNA supercoiling, and causes DNA to cleave. Quercetin encourages DNA scission by forming gyrase-DNA-quercetin cleavable complex. Cleavage of DNA was promoted at quercetin concentration above 80 μM in the presence of gyrase, and at 640 μM the maximum cleavage was obtained [9]. MIC values of quercetin are listed in Table 3. Quercetin obtained from yellow onion skin has inhibitory effect on antibiotic-resistant bacteria H. pylori. Sulfur and quercetin have synergistic growth inhibitory effect with beta lactam, a very functional antibiotic [10].

#### Structure of quercetin

Mode of action of quercetin inhibition includes two mechanisms:

First inhibition pathway involves rivalry at binding site of ATP at gyrase B that prevents DNA supercoiling. The second mechanism involves binding to DNA that

stabilizes DNA topoisomerase II complex causing DNA to cleave [11]. MIC values for different bacterial strains are listed in Table 3.
