title: In vitro cytotoxcity and interaction of new steroidal oxadiazinanones with calf thymus DNA using molecular docking, gel electrophoresis and spectroscopic techniques.
abstract: Herein we report synthesis of new steroidal oxadiazinanones from steroidal ketones. After characterization by spectral and analytical data, the interaction studies of compounds (4-6) with DNA were carried out by UV-vis, fluorescence spectroscopy and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 1.8×10(4) M(-1), 2.2×10(4) M(-1) and 2.6×10(4) M(-1), respectively, indicating the higher binding affinity of compound 6 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compound 6 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. Molecular simulations suggest that compounds binds through minor groove of DNA. MTT assay depicted promising anticancer activity of compound 5 and 6 particularly against HL-60 and MCF-7. The apoptotic degradation of DNA was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). The results revealed that compound 6 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, India. Electronic address: ayazchem09@gmail.com.
authors.forename: Ayaz Mahmood
authors.initials: AM
authors.lastname: Dar
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, India.
authors.forename: Urfi
authors.initials: U
authors.lastname: Ishrat
authors.affiliation: Department of Chemistry, Islamic University of Science & Technology, Pulwama 192122, India.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Yaseen
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202 002, India.
authors.lastname: Shamsuzzaman
authors.affiliation: Department of Biochemistry, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh 202 002, India.
authors.forename: Manzoor Ahmad
authors.initials: MA
authors.lastname: Gatoo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002417:Cattle; D002776:Cholestanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020552:Comet Assay; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis / Q000378:metabolism; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D014783:Viscosity / Q000187:drug effects
chemical_list: C000606299:3-chlorocholestan-6-spiro-1'-oxa-3',4'-diazinan-5'-one; D000970:Antineoplastic Agents; D002776:Cholestanes; D013141:Spiro Compounds; D013256:Steroids; C000606300:cholestan-6-spiro-1'-oxa-3',4'-diazinan-5'-one; D017665:Hydroxyl Radical; D004247:DNA; C427203:calf thymus DNA
keywords: Cyanoacetohydrazide; DNA binding; Docking study; MTT assay; Oxadiazinanone