Margarita Vlachou

A Facile Synthesis of C2-Substituted Pyrrolo[2,3-f]quinolines with Cytotoxic Activity

An expeditious four-step synthesis of the 1H-pyrrolo[2,3-f]quinoline-2- carboxamides (5a-h) is described. Readily available 6-quinolinecarboxaldehyde is converted to the parent acid (6) by nucleophilic attack of the azido-ester (9) and intramolecular cyclization of (10) followed by hydrolysis of the methyl ester (11). The cytotoxicity of the target molecules (5a-h) was evaluated in four tumour cell lines in vitro. One compound (5d) showed sufficient activity (IC50 = 10.2 ?M) in the human non-small cell lung cell line NSCLC-N16-L16 to be worthy of further study.

A New Ring-forming Methodology for the Synthesis of Bioactive Pyrroloquinoline Derivatives

A new, efficient, two-step method for the synthesis of bioactive pyrroloquinolines is described. Readily available nitroquinolines, bearing the nitro moiety in the carbocyclic ring, are treated with 4-chlorophenoxyacetonitrile in the presence of potassium tert-butoxide/THF to give the analogous vicarious nucleophilic substitution products (5, 8 and 11). These, in turn, are subjected to catalytic hydrogenation to produce 1H-pyrrolo[2,3-f]quinoline (6), 3H-pyrrolo[3,2-f]quinoline (9) and 1H-pyrrolo[3,2-h]quinoline (12) in good yields and relatively short reaction times. The differential activity of two N-alkylated 1H-pyrrolo[2,3-f]quinolines (1) in cisplatin resistant cell lines compared to the corresponding parent lines suggests that these might be useful leads for developing agents for use in drug resistant diseases.

An expeditious synthesis of cytotoxic pyrroloisoquinoline derivatives. Structure-activity comparative studies with isomeric pyrroloquinolines.

A number of pyrroloisoquinolines have been prepared by reaction of 5-nitroisoquinoline with vinylmagnesium bromide followed by N-alkylation with the appropriate 2-chloro-N,N-dialkylethylamine. Their cytotoxicity was evaluated in a number of ovarian cell lines and compared to their analogous isomeric pyrroloquinolines. Two of the new compounds, 7c and 7d, are selective toward the A2780 cisplatin-resistant line.

Aromatic polycationic molecules with restricted conformations: An alternative approach to antiherpes agents

A series of aromatic polycationic molecules were synthesised and tested as potential non-classical antiherpes agents. Analogue (4) had a high potency in all four of the HSV cell lines used and is far more potent than ribavirin. The fact that none of the new compounds show any selectivity for HSV-2 over HSV-1 may imply that there is no intervention of a HSV-2 glycoprotein C (gC) dependent pathway.