title: Bioactivity of Marine Streptomyces sp. VITJS4: Interactions of Cytotoxic Phthalate Derivatives with Human Topoisomerase II α: An In Silico Molecular Docking Analysis.
abstract: Despite clinical advances in antimicrobial and anticancer therapy, there is an urge for the search of new bioactive compounds. In the present study, previously isolated Streptomyces sp. VITJS4 strain (NCIM No. 5574) (ACC No: JQ234978.1) crude extract tested for antibacterial activity showed a broad spectrum at the concentration of 20 mg/mL against pathogens. The antioxidant potential tested at 0.5 mg/mL concentration exhibited reducing power activity with a maximum of 90 % inhibition. The anticancer property by MTT assay on HeLa and HepG2 cells showed cytotoxic effect with IC50of 50 µg/mL each. The DNA fragmentation pattern observed in both HeLa and HepG2 cell indicated laddering pattern at 40 µg/mL concentration. GC-MS analysis revealed that the significant peak corresponding at m/z 149 (M+) was identified as phthalate derivatives. The extract was further separated by HPLC with their retention times (tr) at 6.294 min. The above-obtained results were also supported by molecular docking studies which provide an insight into ligand binding to the active site of the receptor. The in silico docking studies revealed better binding affinity with a binding energy of -5.87 kJ mol-1of the ligand toward topoisomerase II α.
authors.affiliation: Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Jemimah Naine
authors.affiliation: Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, India. csubathradevi@vit.ac.in.
authors.forename: C
authors.initials: C
authors.lastname: Subathra Devi
authors.affiliation: Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: V
authors.initials: V
authors.lastname: Mohanasrinivasan
authors.affiliation: Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: C
authors.initials: C
authors.lastname: George Priya Doss
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D059001:Aquatic Organisms / Q000737:chemistry*; D001672:Biocompatible Materials / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures; D053938:DNA Fragmentation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D010795:Phthalic Acids / Q000737:chemistry / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001672:Biocompatible Materials; D045424:Complex Mixtures; D016166:Free Radical Scavengers; D008024:Ligands; D010795:Phthalic Acids; C032279:phthalic acid; D004250:DNA Topoisomerases, Type II
keywords: Bioactive compounds; Cytotoxicity; Marine actinomycetes; Streptomyces sp. VITJS4