title: COMPUTER PREDICTION OF BIOLOGICAL ACTIVITY OF DIMETHYL-N-(BENZOYL)AMIDOPHOSPHATE AND DIMETHYL-N-(PHENYLSULFONYL)AMIDOPHOSPHATE, EVALUATION OF THEIR CYTOTOXIC ACTIVITY AGAINST LEUKEMIC CELLS IN VITRO.
abstract: Structural analogues of β-diketones--dimethyl-N-(benzoyl)amidophosphate (HCP) and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of biological activity and calculation of physicochemical parameters of HCP and HSP compounds were done with the use of PASS and ACD/Labs computer programs. A wide range of biological activity of synthesized compounds, antitumor activity in particular, has been found. Calculations of the bioavailability criteria indicate that the investigated compounds have no deviations from Lipinski's rules. HCP compound is characterized by a high lipophilicity at physiological pH as compared to HSP. It was found that cytotoxic effect of the studied compounds on the leukemic L1210 cells was of time- and dose-dependent character. HCP is characterized by more pronounced and early cytotoxic effects as compared to HSP. It was shown that 2.5 mM HCP increased ROS production 3 times in the early period of incubation, and decreased cell viability by 40% after 48 h, and by 66%--after 72 h. Based on the computer calculation and undertaken research, HCP was selected for target chemical modifications and enhancement of its antitumor effect.
authors.forename: I I
authors.initials: II
authors.lastname: Grynyuk
authors.forename: S V
authors.initials: SV
authors.lastname: Prylutska
authors.forename: N S
authors.initials: NS
authors.lastname: Kariaka
authors.forename: T Yu
authors.initials: TY
authors.lastname: Sliva
authors.forename: O V
authors.initials: OV
authors.lastname: Moroz
authors.forename: D V
authors.initials: DV
authors.lastname: Franskevych
authors.forename: V M
authors.initials: VM
authors.lastname: Amirkhanov
authors.forename: O P
authors.initials: OP
authors.lastname: Matyshevska
authors.forename: M S
authors.initials: MS
authors.lastname: Slobodyanik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D003603:Cytotoxins / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D057927:Hydrophobic and Hydrophilic Interactions; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008956:Models, Chemical; D010755:Organophosphates / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D007659:Ketones; D010755:Organophosphates; D017382:Reactive Oxygen Species