One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic--lasalocid acid.
Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a-2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a-2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC50: 3.2-7.3 μM), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell.
Faculty of Chemistry, Adam Mickiewicz University, Poznan, Poland. adhucz@amu.edu.pl
Adam
A
Huczyński
Jacek
J
Rutkowski
Izabela
I
Borowicz
Joanna
J
Wietrzyk
Ewa
E
Maj
Bogumil
B
Brzezinski
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D007832:Lasalocid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008352:Mannich Bases / Q000737:chemistry*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008352:Mannich Bases; D007832:Lasalocid
Anticancer properties; Antiproliferative activity; BBMULGJBVDDDNI-GTRJCNPJSA-N; BKYSEXHXPZHODW-HOWZEIELSA-N; DFLXPFCTTCQOKF-UHZKBGKTSA-N; KFZXVZRBRBRZMB-VAMONFQJSA-N; Lasalocid acid derivatives; Mannich bases synthesis; NLXPPFVBTOSZOI-VAMONFQJSA-N; Polyether ionophores; SEODYYAZUQDUMA-NBWJWDTASA-N; SHJPPYOZISKIEA-MSCKERGQSA-N; Structural and spectroscopic studies; ZADVVTCFBDWHQX-WRMMZDEISA-N