Design, Synthesis, and Evaluation of (2-(Pyridinyl)methylene)-1-tetralone Chalcones for Anticancer and Antimicrobial Activity

摘要

Background: Chalcones, natural products produced by plants as a natural defensemechanisms against various pathogens, are molecules with structures that include two aromaticrings joined by an α, β unsaturated carbonyl system. Previous research has demonstrated that chalconesexhibit a wide variety of biological activities, including anticancer, antifungal, and antibioticproperties.Objective: Our goal is to synthesize novel heterocyclic-containing chalcones and have their biologicalactivities evaluated.Methods Sixteen chalcones were synthesized by the crossed aldol condensation of substitutedtetralones with substituted pyridinylaldehydes. The products were purified by recrystallization inMeOH/H2O and characterized by 1H NMR, 13C NMR, and HRMS. Anticancer assays were performedby NCI (National Cancer Institute) against the NCI-60 panel of 60 different human cancercell 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, Klebsiellapneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Cryptococcusneoformans var. grubii, and Candida albicans.Result: Chalcone 3d had demonstrated growth inhibition greater than 60% against a variety ofcancers: 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 cytotoxicto 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 ofMRSA by 75%. 3b was the best compound against EC, KP, and PA and 3f had the greatest activityagainst AB. For fungi, 3f and 3e demonstrated the best growth inhibition.Conclusion: A small library of heterocyclic-containing chalcones was developed and initialscreening demonstrates modest activity against cancers, bacteria, and fungi.