Antibacterial and Cytotoxicity of Extracts and Isolated Compounds from : A Combined Experimental and Computational Study.

is a widely cultivated hedge plant in Ethiopia. Traditionally, they have been used to treat a variety of health conditions, including intestinal problems, infectious diseases, tonsillitis, and leishmaniasis. Silica gel chromatographic separation of the methanol and ethyl acetate extracts of the leaves, roots, and stem barks of led to the isolation of 12 compounds, labeled as 1-12. Among these, compounds 1, 3, 4, 5, and 7-11 are reported as new to the genus . The extracts and isolated compounds from were evaluated for their in vitro antibacterial activity against four bacterial strains: , , , and , using the disc diffusion assay. All of the extracts displayed weak antibacterial activity, with inhibition zone diameters (IZDs) ranging from 6.10 ± 0.3 to 9.30 ± 0.20 mm. The isolated compounds, on the other hand, exhibited weak to moderate antibacterial activity, with IZDs ranging from 6.00 ± 0.300 to 13.50 ± 0.50 mm. The most potent antibacterial activity was observed for compound 6, which showed an IZD of 13.30 ± 0.50 mm against and 13.50 ± 0.50 mm against . This activity was comparable to that of the positive control ceftriaxone, which had IZDs of 14.1 ± 0.3 and 13.8 ± 0.5 mm against and , respectively. The in silico molecular docking analysis against DNA gyrase B revealed that compound showed a higher binding affinity (-6.9 kcal/mol), followed by compound (-6.7 kcal/mol) and compound (-6.3 kcal/mol), whereas ciprofloxacin showed -7.3 kcal/mol. The binding affinities of compounds , , , and were found to be -5.0, -4.3, -4.2, and -4.0 kcal/mol against Pyruvate kinase, respectively, whereas ciprofloxacin showed a binding affinity of -4.9 kcal/mol, suggesting that compound had a better binding affinity compared with ciprofloxacin. The effect of extracts of was evaluated for cytotoxic activity against the breast cancer cell line (MCF-7) by the MTT assay. The extracts induced a decrease in cell viability and exerted a cytotoxic effect at a concentration of 20 μg/mL. The highest percent cell viability was observed for the methanol extract of the stem (92.9%), whereas the least was observed for the methanol extract of the root (34.5%). The result of the latter was significant compared with the positive control. The binding affinities of the isolated compounds were also assessed against human topoisomerase inhibitors IIβ. Results showed that compound showed a binding affinity of -6.0 kcal/mol, followed by (-5.4 kcal/mol), (-5.0 kcal/mol), and (-4.9 kcal/mol). Similar to ciprofloxacin, compounds , , , , , and comply with Lipinski's rule of five. Overall, the comprehensive investigation of the chemical constituents and their biological activities reinforces the traditional medicinal applications of and warrants further exploration of this plant as a source of novel therapeutic agents.