Tag Archives: PASS-prognosis

Computer prediction of biological activity of dimethyl-N-(benzoyl)amidophosphate and dimethyl-N-(phenylsulfonyl)amidophosphate, evaluation of their cytotoxic activity against leukemia cells in vitro

I. I. Grynyuk, S. V. Prylutska, N. S. Kariaka, T. Yu. Sliva,
O. V. Moroz, D. V. Franskevych, V. M. Amirkhanov,
O. P. Matyshevska, M. S. Slobodyanik

Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: igrynyuk@yahoo.com

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 leukemiс 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.

Antioxidant activity of alkoxy derivatives of (quinoline-4-ylthio)carboxylic acids

O. О. Brazhko1, M. P. Zavgorodny1, O. S. Kruglyak2,
L. O. Omeljanchik1, G. A. Shapoval2

1Zaporizhzhya National University, Ukraine;
2Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: hellen.brazhko@gmail.com

A selection of potential bioactive molecules including alkoxy derivatives of (quinoline-4-ylthio)carboxylic acids using virtual screening has been carried out and their biological activity was determined. The studied substances proved to be low-toxic, biologically active compounds. It was established that 4-thio derivatives of quinoline exhibit pronounced antiradical, antioxidant effects and can act as preventive antioxidants, radio and cytoprotectors.