The effect of heterocyclic substituent at C-3 position of 1-(4-methyl-piperazin-1-yl)isoquinolines on their anticancer activity

Abstract

A comparative analysis of the anti-cancer activity of 1-(4-methylpiperazin-1-yl)isoquinolines with different heteroaromatic substituents in С-3 position: 2-methylthiazol-4-yl, 2-phenylthiazol-4-yl, 2-(pyridin-4-yl)thiazol-4-yl, imidazo[2,1-b]thiazol-6-yl, quinoxalin-2-yl, 6,7-dimethylquinoxalin-2-yl. Methods. Biological tests; statistic methods. Results. In vitro screening of the anticancer activity showed that the derivatives with 2-phenylthiazol-4-yl, quinoxaline-2-yl, 6,7-dimethylquinoxalin-2-yl substituents demonstrated the highest level of anticancer activity; however, they were inferior to 2-(pyridin-4-yl)thiazol-4-yl. The product with the 2-methylthiazol-4-yl residue almost did not demonstrated cytotoxicity. Comparative analysis showed no significant correlation with known drugs; hence these compounds have specific molecular targets. Conclusions. The resulting 1-amino-3-hetarylisoquinolines are a promising class of compounds for anticancer drug development. The level and direction of the activity significantly depend on the nature of heterocyclic substituents. K e y w o r d s: in vitro screening, anticancer activity, 1-amino-3-hetarylisoquinolines.

Distinctive Features of 3‐Acetyl‐ and 3‐Benzoyl‐Isocoumarins’ Interaction with Active Primary Amines

“…[5,6] One step involved in the synthesis of the latter was the recyclization of 3hetarylisocoumarins into the corresponding isoquinolin-1-ones. [5][6][7] These reactions are of significant interest as they offer more possibilities for further synthetic transformations. Numerous functional groups are tolerant of this transformation, and these fragments are primarily located far from the reaction center.…”

“…Notably, many isoquinolines with active functional groups and useful properties can be obtained via the recyclization of isocoumarins using ammonia, primary amines, and other nucleophiles with an NH 2 group (e. g., hydrazine, hydroxylamine). Recent achievements in this field include the synthesis of 2‐R‐5‐(acylamino)isoquinolin‐1(2 H )‐ones, which are modulators of the P2X7 receptor (Scheme 1a), [2] 2,3,6‐trisubstituted 1‐oxo‐1,2‐dihydroisoquinolines as potent CRTh2 antagonists (Scheme 1b), [3] new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons (Scheme 1c), [4] and a convenient approach to the synthesis of 1‐amino‐3‐hetarylisoquinolines with anticancer activity (Scheme 1d) [5,6] . One step involved in the synthesis of the latter was the recyclization of 3‐hetarylisocoumarins into the corresponding isoquinolin‐1‐ones [5–7] .…”

“…Recent achievements in this field include the synthesis of 2-R-5-(acylamino)isoquinolin-1(2H)-ones, which are modula-tors of the P2X7 receptor (Scheme 1a), [2] 2,3,6-trisubstituted 1oxo-1,2-dihydroisoquinolines as potent CRTh2 antagonists (Scheme 1b), [3] new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons (Scheme 1c), [4] and a convenient approach to the synthesis of 1-amino-3-hetarylisoquinolines with anticancer activity (Scheme 1d). [5,6] One step involved in the synthesis of the latter was the recyclization of 3hetarylisocoumarins into the corresponding isoquinolin-1-ones. [5][6][7] These reactions are of significant interest as they offer more possibilities for further synthetic transformations.…”