<i>In vitro</i> antibacterial and antioxidant activity of flavonoids from the roots of <i>Tephrosia vogelii</i>: a combined experimental and computational study

Abstract

<i>Tephrosia vogelii</i> is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH₂Cl₂/MeOH (1:1) roots extract of <i>T. vogelii</i> afforded seven compounds namely; β-sitosterol (<b>1a</b>), stigmasterol (<b>1b</b>), 6a, 12a-dehydro-deguelin (<b>2</b>), tephrosin (<b>3</b>), maackiain (<b>4</b>), obovatin (<b>5</b>) and 6-oxo, 6a, 12a-dehydro-deguelin (<b>6</b>). GC-MS analysis of essential oils from the root of <i>T. vogelii</i> displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CH₂Cl₂/MeOH (1:1) extract, MeOH extract, maackiain (<b>4</b>) and obovatin (<b>5</b>) showed moderate inhibitory activity against <i>Pseudomonas aeruginosa</i> with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 μg/mL). 6a, 12a-dihydro-deguelin (<b>2</b>), and 6-oxo, 6a, 12a-dehydro-deguelin (<b>6</b>) displayed significant activity against <i>S. epidermis</i> with MIC values of 0.66 mg/mL. Tephrosin (<b>3</b>) and maackiain (<b>4</b>) also showed moderate antibacterial activity against <i>Staphylococcus aureus</i> and <i>Proteus mirabilis</i> with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 μg/mL). The radical scavenging activity results indicated that tephrosin (<b>3</b>), obovatin (<b>5</b>) and 6-oxo, 6a, 12a-dehydro-deguelin (<b>6</b>) showed potent DPPH scavenging activity with IC₅₀ values of 10.97, 10.43 and 10.73 μg/mL, respectively, compared to ascorbic acid (IC₅₀ of 5.83 μg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin (<b>2</b>) displayed the best binding energy of -8.1 kcal/mol towards pyruvate kinase of <i>S. aureus</i> (PDB ID: 3T07) and -7.9 kcal/mol towards <i>P. mirabilis</i> urease (PDB ID: 1E9Y) and DNA gyrase B of <i>Escherichia coli</i> (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to -8.0 kcal/mol). Maackiain (<b>4</b>) and obovatin (<b>5</b>) displayed the minimum binding energy of -7.9 and -8.2 kcal/mol towards the LasR protein of <i>P. aeruginosa</i> (PDB: ID 2UV) and <i>S. epidermidis</i> FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (<b>2</b>-<b>6</b>) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The <i>in vitro</i> assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of <i>T. vogelii</i>.