Characterization of soil-derived Bacillus subtilis metabolites against breast cancer: In vitro and in silico studies

土壤来源枯草芽孢杆菌代谢产物抗乳腺癌特性研究:体外和计算机模拟研究

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Abstract

Breast cancer remains one of the most challenging and widespread cancers among women globally that warrants further investigations for novel agents to minimize side effects and disease recurrence. In this study, a soil bacterium was isolated and 16S rRNA nucleotide sequence homology and resultant phylogenetic tree analysis confirmed Bacillus subtills (CP020102.1). The crude extract of bacterial strain showed cytotoxicity (cell viability 63.1%) against human breast cancer cell line MCF-7 through MTT assay followed by further analysis through preparative HPLC showing 29 active fractions. Among all fractions, fraction 16 demonstrated cytotoxic potential as low as 54.03%. The spectral data of LC-MS, NMR and FTIR identified the bioactive compound as isatin based bacterial metabolite (Z)-N'-(1-hexyl-2-oxoindolin-3-ylidene)-4-methylbenzenesulfonohydrazide. This bioactive compound upon in silico docking analysis with HER2 showed a binding energy of -8.8 kcal/mol. ADMET calculations determined the pharmacokinetic behavior of the compound revealing acceptable distribution and absorption profiles. The drug-likeness of the compound was confirmed based on the Lipinski rule with zero violations. Molecular dynamic simulation (MDS) was also performed for 100 ns and a stable RMSF plot was observed. The results strongly propose that the identified compound has immense potential to be considered a drug candidate to develop further against human breast cancer.

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