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Abstract
The undertaken research has been realized in two fundamental areas: indoles as novel antibacterial agents and versatile precursors of complex heterocyclic structures. Several classes of structurally related hydrazine-linked bis-indoles were synthesized and evaluated towards inhibition of bacterial transcription initiation complex formation. The compounds were found to efficiently inhibit the β'-σ70/σA interaction essential for RNA polymerase holoenzyme formation as well as the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were carried out in order to identify the structural features of the synthesized inhibitors potentially required for biological activity. Structurally related scaffolds were explored as well. Synthesis and evaluation of antibacterial activity of a variety of mono-indole-, mono-benzofuran-, bis-indolylmethane- and tetra-indole-based carbox- and glyoxyloylamides, and carbo- and glyoxyloylhydrazides demonstrated that significant reduction in molecule size resulted in not only solubility enhancement, but also in retention of biological activity both at the level of inhibition of the β′-σ70/σA interaction and bacterial growth in culture. Chemistry of 2,7'-bi-indolyls has been developed in two main directions. Functionalization of the position 7 of the 2,7'-bi-indolyl scaffold resulted in the synthesis of carbohydrazides and glyoxyloylamides. Vilsmeier-Haack-type reactions taking place at position 7 were investigated as well. Stability of 2,7'-bi-indolyls in the presence of strong bases was explored and the unusual ring opening reaction observed. Efficient and regioselective procedures for bromination of 2,7'-bi-indolyls and quinazolin-7-ones using bromine and N-bromosuccinimide were developed to afford a wide range of novel mono-, di-, tri- and tetrabrominated derivatives. New method for the synthesis of macrocyclic tetra-indolyls via acid-catalyzed coupling of the 2'-bromo-2,7'-bi-indolyl was reported and a possible mechanism of the reaction presented. The structures of numerous quinazolin-7-one derivatives were supported by single crystal X-ray crystallography. 1,2,4,5-Tetrafluorobenzene and pentafluorobenzene were reacted with indoles and pyrrole to give the corresponding mono- and polysubstituted benzenes. An attempt was made to oxidize these molecules to azacoronenes.