Prediction of the biological activity of aminomethansulfonic acid derivatives

Abstract

The targeted synthesis of the new compounds including aminomethansulfonic acid (AMSA) derivatives remains one of the most promising way of the medicines development. The aim of the research was an analysis of the biological and pharmacological activity of AMSA derivatives by PASS programm. The evaluation of supposed biological activity among AMSA derivatives has been conducted by PASS analysis (Prediction of Activity Spectra for Substances). The index Ра (probability) from 0,7 to 1,0 proves a high probability of the corresponding activity. The following compounds have been studied: N-(2hydroxyethyl)-AMSA (HEAMSA), N-(propyl)-AMSA (PrAMSA), N-(buthyl)-AMSA (BuAMSA), N-(tretbuthyl)-AMSA (tBuAMSA), N-(heptyl)-AMSA (HpAMSA), 4-(N-phenylaminomethyl)-phenyl-AMSA (PhAMPhAMSA), N-(benzyl)-AMSA (BzAMSA). According to the results obtained four compounds (HEAMSA > BzAMSA > PrAMSA > tBuAMSA; Pa = 0,702…0,822) showed a putative potency to inhibit an enzyme glycosylphosphatidylinositol phospholipa se D that could be associated with a capacity to inhibit tumor and stem cells growth. Compounds HEAMSA, PrAMSA, BuAMSA, tBuAMSA, HpAMSA demonstrated supposed ability to inhibit an enzyme exoribonuclease II, which can determine an antiviral activity. Almost all studied compounds could inhibit the enzymes endoglycosylceramidase and sugar-phosphatase that can lead to hypoglycemic action. In addition, by the last activity with Ра = 0,732…0,815 according to potency the compounds can be ranged as follows: HpAMSA > BuAMSA > PrAMSA > HEAMSA > tBuAMSA > BzAMSA. For all studied АМSA compounds, except BzAMSA, the antihypoxic activity is predicted. According to antihypoxic potency compounds can be ranged as follows: BuAMSA > HpAMSA > HEAMSA > PrAMSA > tBuAMSA > PhAMPhAMSA (Pa = 0,705…0,814), compounds HEAMSA and PrAMSA can cause an anxiolytic action, compound tBuAMSA – analgesic action, PhAMPhAMSA – antipyretic action, compounds BuAMSA, HpAMSA can inhibit pro-opiomelanocortin (РОМС) converting enzyme. РОМС is a prohormone, from which adrenocorticotropic and melanocyte-stimulating hormones can be formed as well as beta-lipotropin and bеtаendorphin. That is why the inhibition of РОМС breakdown may have an impact on endocrinic and antinociceptive system.