title: 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.
abstract: 4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization.
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors: Manohar
authors: M
authors: Puppala
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA; College of Traditional Chinese Veterinary Medicine, Agricultural University of Hebei, Baoding, Hebei 071001, People's Republic of China.
authors: Xinghua
authors: X
authors: Zhao
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors: Denise
authors: D
authors: Casemore
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors: Bo
authors: B
authors: Zhou
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA; LG Life Sciences Ltd, 104-1, Munji-dong, Yuseong-gu, Daejeon 305-380, South Korea.
authors: Gopalakrishnan
authors: G
authors: Aridoss
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA.
authors: Sreekanth
authors: S
authors: Narayanapillai
authors: Department of Medicinal Chemistry, University of Minnesota, 2231 6th Street SE, Minneapolis, MN 55455, USA. Electronic address: xingx009@umn.edu.
authors: Chengguo
authors: C
authors: Xing
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans
keywords: 4H-Chromene; Anticancer; Cytotoxicity; Multi-drug resistant; Structure–activity relationship