Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure startingfrom the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562 cells.Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative17b showed a better antitumoral effect on K562 cells than 13b and 14b. Analyses performed to explore17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequentto DNA lesions as demonstrated by the increase in phospho-ATM and gH2AX, two known markers ofDNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK andinduction of caspase-3 dependent apoptosis.
|Numero di pagine||12|
|Rivista||European Journal of Medicinal Chemistry|
|Stato di pubblicazione||Published - 2017|
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry
Raffa, D., Maggio, B., Lauricella, M., Daidone, G., Raimondi, M. V., D'Anneo, A., & Plescia, F. (2017). Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action. European Journal of Medicinal Chemistry, 132, 262-273.