NOVEL NORTOPSENTIN ANALOGUES: PYRROLO[2,3-b]PYRIDINE,bis(PYRROLO[2,3-b]PYRIDINE AND 7 -CHLORO-PYRROLO[2,3-c]PYRIDINE ANALOGUES

Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues.

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contr…

SYNTHESIS OF PYRROLO[2,3-b]PYRIDINE, BIS(PYRROLO[2,3-b]PYRIDINE) and 7-CHLORO-PYRROLO[2,3-c]PYRIDINE, ANALOGUES OF MARINE BIS(INDOLE)ALKALOID NORTOPSENTIN

Synthesis of Nortopsentin analogues

Discovery of new G-quadruplex binding chemotypes

We report here on the discovery and preliminary evaluation of a novel non-macrocyclic low molecular weight quadruplex-stabilizing chemotype. The lead compounds, based on a furan core, show high G-quadruplex stabilisation and selectivity as well as potent in vitro anti-proliferative activity.

Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3- b]pyridines, indolyl-thiazolyl-pyrrolo[2,3-b]pyridines and indolylthiazolyl- pyrrolo[2,3-c]pyridines, nortopsentin analogues

3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunctio…