412
P. M. Vassiliev et al.
3. 68 compounds (67.3 % of those with high-level activity) are comparable to or
exceed the activity of comparison drugs; 30 of them (44.1 %) are more active
than the drugs for comparison;
4. The effectiveness of the search for compounds with an expressed activity was
2.07 times higher, and for those with a high activity, it was 3.49 times higher, in
comparison to a prediction without IT Microcosm.
Therefore, the complex methodology of predicting the pharmacological activity
employed in IT Microcosm and comprising a consensus approach to prediction as
one of its constituent parts proved to be effective in a search for novel drugs among
condensed azole derivatives of 15 different chemical classes.
12.5 IT Microcosm in Prediction of Pharmacological
Activity of Complex Molecular Systems and of Their
Component Synergism
Prediction of the biological activity of unconventional chemical structures is one of
the most challenging problems faced by QSAR. In particular, such unconventional
systems encompass organic salts, including those with organic acids and bases,
supramolecular complexes formed by noncovalent intermolecular interactions between certain compounds and mixtures containing several individual substances.
To make a successful in silico assessment of the pharmacological activity of such
complex chemical constructs, one should consider both their qualitative and quantitative composition as well as the mutual effect of the components constituting these
systems, in particular, the synergistic effects. The QL language in IT Microcosm
provides an option of taking into account the noncovalent interactions [110] and
making a successful prediction of the biological activity of complex molecular systems [35, 74, 75, 97, 105, 111, 112, 114, 119, 120, 123, 128, 129].
12.5.1 Organic Salts
Varying the salt-forming residue is a common method in drug design. Several
examples are the antitussive drug Codeine (manufactured as a hydrochloride or
a phosphate), the spasmolytic drug Prenoverine (in the form of a citrate) and the
antibiotic Fumagillin (dicyclohexylammonium salt). A salt of a complex organic
compound can be likened to a complete supramolecular system because the stability
in both cases is achieved through noncovalent interactions.
The results of using IT Microcosm for predicting the presence/absence or the
level of various types of pharmacological activity among the structurally similar
and structurally diverse compounds discussed in Sect. 3 were obtained for the salts
of those compounds; the salt-forming residue associated with the main chemical
structure was used in the computations [105, 109, 123]. In the sets, there were salts
of the main inorganic acids (HCl, HBr, HNO 3 , H 2 SO 4 , H 3 PO 4 , HClO 4 ), of various
P. M. Vassiliev et al.
3. 68 compounds (67.3 % of those with high-level activity) are comparable to or
exceed the activity of comparison drugs; 30 of them (44.1 %) are more active
than the drugs for comparison;
4. The effectiveness of the search for compounds with an expressed activity was
2.07 times higher, and for those with a high activity, it was 3.49 times higher, in
comparison to a prediction without IT Microcosm.
Therefore, the complex methodology of predicting the pharmacological activity
employed in IT Microcosm and comprising a consensus approach to prediction as
one of its constituent parts proved to be effective in a search for novel drugs among
condensed azole derivatives of 15 different chemical classes.
12.5 IT Microcosm in Prediction of Pharmacological
Activity of Complex Molecular Systems and of Their
Component Synergism
Prediction of the biological activity of unconventional chemical structures is one of
the most challenging problems faced by QSAR. In particular, such unconventional
systems encompass organic salts, including those with organic acids and bases,
supramolecular complexes formed by noncovalent intermolecular interactions between certain compounds and mixtures containing several individual substances.
To make a successful in silico assessment of the pharmacological activity of such
complex chemical constructs, one should consider both their qualitative and quantitative composition as well as the mutual effect of the components constituting these
systems, in particular, the synergistic effects. The QL language in IT Microcosm
provides an option of taking into account the noncovalent interactions [110] and
making a successful prediction of the biological activity of complex molecular systems [35, 74, 75, 97, 105, 111, 112, 114, 119, 120, 123, 128, 129].
12.5.1 Organic Salts
Varying the salt-forming residue is a common method in drug design. Several
examples are the antitussive drug Codeine (manufactured as a hydrochloride or
a phosphate), the spasmolytic drug Prenoverine (in the form of a citrate) and the
antibiotic Fumagillin (dicyclohexylammonium salt). A salt of a complex organic
compound can be likened to a complete supramolecular system because the stability
in both cases is achieved through noncovalent interactions.
The results of using IT Microcosm for predicting the presence/absence or the
level of various types of pharmacological activity among the structurally similar
and structurally diverse compounds discussed in Sect. 3 were obtained for the salts
of those compounds; the salt-forming residue associated with the main chemical
structure was used in the computations [105, 109, 123]. In the sets, there were salts
of the main inorganic acids (HCl, HBr, HNO 3 , H 2 SO 4 , H 3 PO 4 , HClO 4 ), of various