Gibson Maya Z, Nguyen Minh A, Zingales Sarah K
Department of Chemistry & Physics, Georgia Southern University, Savannah, GA, United States.
Med Chem. 2018;14(4):333-343. doi: 10.2174/1573406413666171020121244.
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 properties.
Our goal is to synthesize novel heterocyclic-containing chalcones and have their biological activities evaluated. 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.
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.
A small library of heterocyclic-containing chalcones was developed and initial screening demonstrates modest activity against cancers, bacteria, and fungi.
查耳酮是植物产生的天然产物，作为抵御各种病原体的天然防御机制，是一类分子，其结构包括由α，β不饱和羰基系统连接的两个芳香环。先前的研究表明，查耳酮具有多种生物活性，包括抗癌、抗真菌和抗菌特性。
我们的目标是合成新型含杂环查耳酮并评估其生物活性。方法 通过取代四氢萘酮与取代吡啶醛的交叉羟醛缩合反应合成了16种查耳酮。产物通过在甲醇/水中重结晶进行纯化，并通过1H NMR、13C NMR和高分辨质谱进行表征。美国国立癌症研究所（NCI）针对包括白血病、非小细胞肺癌、结肠癌、中枢神经系统癌、黑色素瘤、卵巢癌、肾癌、前列腺癌和乳腺癌在内的60种不同人类癌细胞系的NCI-60细胞株进行了抗癌试验。开放抗微生物药物发现协会（COADD）针对大肠杆菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌、金黄色葡萄球菌、新型隐球菌格鲁比变种和白色念珠菌进行了抗菌试验。
查耳酮3d对多种癌症表现出大于60%的生长抑制作用：白血病（MOLT-4、SR）、非小细胞肺癌（NCI-H522）、结肠癌（HCT-116）、前列腺癌（DU-145）和乳腺癌（MCF7、MDA-MB-468），并且对三种不同细胞系（CCRF-CEM、RPMI-8226和KM12）也具有细胞毒性。5c对白血病（CCRF-CEM、RPMI-8226、SR）和乳腺癌（MCF7）有活性，5e仅对白血病（RPMI-8226、SR）有活性。5h有部分活性，是对耐甲氧西林金黄色葡萄球菌生长抑制率达75%的最佳化合物。3b是对抗大肠杆菌、肺炎克雷伯菌和铜绿假单胞菌的最佳化合物，3f对鲍曼不动杆菌的活性最大。对于真菌，3f和3e表现出最佳的生长抑制作用。
构建了一个含杂环查耳酮的小型文库，初步筛选表明其对癌症、细菌和真菌具有一定活性。
