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Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action.
- Source :
-
European Journal of Medicinal Chemistry . May2017, Vol. 132, p262-273. 12p. - Publication Year :
- 2017
-
Abstract
- Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f , 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11 , the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f . Derivatives 13a-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. Derivative 17b showed a better antitumoral effect on K562 cells than 13b and 14b . Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CARBOXAMIDES
*PHOSGENE
*CHEMICAL derivatives
*CELL cycle
*DNA repair
*APOPTOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 132
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 122528381
- Full Text :
- https://doi.org/10.1016/j.ejmech.2017.03.051