Inhibition of the ATPase Domain of Human Topoisomerase IIa on HepG2 Cells by 1, 2-benzenedicarboxylic Acid, Mono (2-ethylhexyl) Ester: Molecular Docking and Dynamics Simulations.

BACKGROUND: The major attention has been received by the natural products in the prevention of diseases due to their pharmacological role. OBJECTIVE: The major focus of the study was to search for highly potential anti-cancer compounds from marine Streptomyces sp. VITJS4 (NCIM No. 5574). METHODS: Cytotoxic assay was examined by MTT assay on HepG2 cells. Bioassay-guided fractionation of the ethyl acetate extract from the fermented broth led to the isolation of the compound. The lead compound structure was elucidated by combined NMR and MS analysis, and the absolute configuration was assigned by extensive spectroscopic analysis. RESULTS: On the basis of spectroscopic data, the compound was identified as 1, 2 benzenedicarboxylic acid, mono 2-ethylhexyl (BMEH). The compound exhibited in vitro anticancer potential against liver (HepG2) cancer cells. Based on the flow cytometric analysis, it was evident that the BMEH was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of Bcl-2 family proteins, and activation of caspase-9 and 3. The molecular docking and dynamics simulation were performed to reveal the activity of the compound over a time period of 10ns. From the molecular dynamics studies, it was found that the stability and compactness were attained by the protein by means of the compound interaction. CONCLUSION: This study highlights our collaborative efforts to ascertain lead molecules from marine actinomycete. This is the first and foremost report to prove the mechanistic studies of the purified compound 1, 2-benzene dicarboxylic acid, mono(2-ethylhexyl) ester isolated from marine Streptomyces sp.VITJS4 against HepG2 cells.

Bio Prospecting of Marine-derived Streptomyces spectabilis VITJS10 and Exploring its Cytotoxicity Against Human Liver Cancer Cell Lines.

BACKGROUND: Recently, numerous pathogens have developed resistance due to the indiscriminate use of commercial therapeutic drugs. OBJECTIVE: The main aim of the study was to evaluate the bioactive potential of the Streptomyces spectabilis VITJS10 crude extract. MATERIALS AND METHODS: The S. spectabilis VITJS10 ethyl acetate extract was tested for antibacterial, antioxidant, and cytotoxic properties. Genotypic characterization was done using 16S r-DNA partial gene amplification and sequencing. The authenticity of the crude chemical constitutes were determined by gas chromatography-mass spectrometry (GC-MS). RESULTS: The antibacterial potential revealed the effective activity against Shigellaflexneri (MTCC No: 1457) (22 mm), Salmonella typhi (MTCC No: 1167) (23 mm), Escherichia coli (MTCC No: 1588) (22 mm), Pseudomonas aeruginosa (MTCC No: 4676) (22 mm) at 20 mg/mL concentration. Scavenging ability of the extract was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealing its 95% inhibition at 5 mg/mL concentration. Hepatocellular cancer cells (HepG2) cell line was used to evaluate the cytotoxicity by 3-(4, 5-dimethyl thiazol-2yl)-2, 5-diphenyl tetrazolium bromide assay. The extract showed maximum inhibition at IC50 of 250 µg/mL with 53.6% cell viability. The highest 16S rRNA gene sequence homogeneity was observed 99% similar with the novel strain S. spectabilis S3-1. The chemical components of the crude extract of VITJS10 were detected with 37 chemical constituents. However three major compounds were identified, namely Sulfurous acid, 2-ethylhexyl tridecyl ester, Phenol, 2,4-bis (1,1-dimethylethyl), and Trans-2-methyl-4-n-pentylthiane, S, S-Dioxide. CONCLUSION: Hence the present study justifies the overwhelming circumstantial evidence as the most bioactive metabolites from the marine origin, which has potential utilization in pharmaceutical industry. SUMMARY: The aim of this study was to explore the bioactive potential of marine Streptomyces sp. isolated from marine soil and understand the bioactive properties of the crude extracts. It is clearly evident from the study that the bioactive metabolites produced by Streptomyces sp. exhibited good antibacterial, antioxidant and anticancer activity. Our results indicated that Starch casein medium was the good base for bioactive metabolite production. The taxonomic position of Streptomyces sp. isolated revealed unique pattern of phenotypic properties that distinguished it from representatives. The molecular characterization results provided valuable data for establishing the internal taxonomic structure of the genus. Hence high mortality rates, serious side effects, deficiencies of the available chemotherapeutics, and high costs during treatment clearly underscore the need to develop new anticancer agents, With the above significant features the strain could be recommended for its use in medicinal and agricultural sectors, an extensive knowledge on the behavior of natural compounds can be gained for the benefit of health.