Background: Chalcones, natural products produced by plants as a natural defense
mechanisms against various pathogens, are molecules with structures that include two aromatic
rings joined by an α, β unsaturated carbonyl system. Previous research has demonstrated that chalcones
exhibit a wide variety of biological activities, including anticancer, antifungal, and antibiotic
Objective: Our goal is to synthesize novel heterocyclic-containing chalcones and have their biological
Methods Sixteen chalcones were synthesized by the crossed aldol condensation of substituted
tetralones with substituted pyridinylaldehydes. The products were purified by recrystallization in
MeOH/H2O and characterized by 1H NMR, 13C NMR, and HRMS. Anticancer assays were performed
by NCI (National Cancer Institute) against the NCI-60 panel of 60 different human cancer
cell lines, including leukemia, non-small-cell lung cancer, colon, central nervous system, melanoma,
ovarian, renal, prostate, and breast cancer. Antimicrobial assays were performed by COADD
(Community for Open Antimicrobial Drug Discovery) against Escherichia coli, Klebsiella
pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Cryptococcus
neoformans var. grubii, and Candida albicans.
Result: Chalcone 3d had demonstrated growth inhibition greater than 60% against a variety of
cancers: leukemia (MOLT-4, SR), non-small cell lung cancer (NCI-H522), colon cancer (HCT-
116), prostate cancer (DU-145), and breast cancer (MCF7, MDA-MB-468) and was also cytotoxic
to three different cell lines (CCRF-CEM, RPMI-8226, and KM12). 5c was active against leukemia
(CCRF-CEM, RPMI-8226, SR) and breast cancer (MCF7) and 5e was active only against leukemia
(RPMI-8226, SR). 5h was partially active and the best compound with growth inhibition of
MRSA by 75%. 3b was the best compound against EC, KP, and PA and 3f had the greatest activity
against AB. For fungi, 3f and 3e demonstrated the best growth inhibition.
Conclusion: A small library of heterocyclic-containing chalcones was developed and initial
screening demonstrates modest activity against cancers, bacteria, and fungi.