Open AccessIdentification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities
Author(s) -
Seung-Ha Oh,
Do Yoon Kwon,
Inhee Choi,
Young Mi Kim,
Ji Young Lee,
Jiyoung Ryu,
Hangyeol Jeong,
Myung Jin Kim,
Rita Song
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00570
Subject(s) - carboxamide , senescence , melanoma , in vitro , cytotoxicity , phenotype , piperidine , phenotypic screening , chemistry , small molecule , computational biology , identification (biology) , high content screening , cancer research , pharmacology , medicine , biology , biochemistry , cell , microbiology and biotechnology , stereochemistry , gene , botany
This study evaluated the potential use of senescence-inducing small molecules in the treatment of melanoma. We screened commercially available small-molecule libraries with high-throughput screening and high-content screening image-based technology. Our findings showed an initial hit with the embedded N -arylpiperidine-3-carboxamide scaffold-induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. A focused library containing diversely modified analogues were constructed and examined to evaluate the structure-activity relationship of N -arylpiperidine-3-carboxamide derivatives starting from hit 1 . This work identified a novel compound with remarkable antiproliferative activity in vitro and demonstrated the key structural moieties within.