Andrejus Korolkovas

Conformational analysis of the 1,4-dihydropyridines linking the structural aspects to the biological binding event: a study of the receptor-site conformation

Abstract A conformational analysis involving a set of 45 2,6-dimethyl-3,5-dicarbomethoxy-4-X-phenyl-1,4-dihydropyridine derivatives was performed. The potential energy surfaces of the rotation of the phenyl ring around the pyridine ring were constructed for each compound. These were arranged in groups of five in descending order of biological activity. The energy level below 99% of the molecular population for each molecule was superimposed on those groups. The conformationally stable regions permitted to this molecular population were found and compared. The analysis of each group of potential energy surfaces thus constructed revealed that in the biologically active conformation the phenyl ring bisects the pyridine ring and the ortho/meta phenyl substituents are spatially away from the pyridine ring.

Antimalarial activity of saccharidic polymers of dapsone and sulfadimethoxine.

With the purpose of obtaining pro-drugs of dapsone and sulfadimethoxine, those chemotherapeutic agents were attached through covalent bonding to starch polymeric dialdehyde (Sumstar-190). The antimalarial activity of the two resulting compounds - the dapsone saccharidic polymer (PS6) and the sulfadimethoxine saccharidic polymer (PS7) - in mice experimentally inoculated with Plasmodium berghei was significantly increased with this molecular modification. Mice infected with malaria and kept without treatment together with others which received different doses of PS6 and PS7 were also partially or totally cured, possibly due to the ingestion of excrements containing the parent chemotherapeutic agents.