The enone motif of (+)-grandifloracin is not essential for 'anti-austerity' antiproliferative activity.
We report the synthesis and biological evaluation of three analogues of the natural product (+)-grandifloracin (+)-1. All three analogues exhibit enhanced antiproliferative activity against PANC-1 and HT-29 cells compared to the natural product. The retention of activity in an analogue lacking the enone functional group, 9, implies this structural element is not an essential part of the (+)-grandifloracin pharmacophore.
Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Monika
M
Ali Khan
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.
Pauline J
PJ
Wood
Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Natasha M
NM
Lamb-Guhren
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.
Lorenzo
L
Caggiano
Crystallography Unit, Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Gabriele
G
Kociok-Köhn
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.
David
D
Tosh
Department of Chemistry, University of Bath, Bath BA2 7AY, United Kingdom. Electronic address: S.E.Lewis@bath.ac.uk.
Simon E
SE
Lewis
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D031046:Uvaria / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D007659:Ketones; C560843:grandifloracin
Analogue synthesis; Antiproliferative; Natural products; Organoiron chemistry; Pancreatic cancer