Abstract：
New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 μM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 μM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 μg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 μg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.
摘要：
新的吡啶基查耳酮4a-h和吡唑啉5a-h（N-乙酰基），6a-h(N-苯基),和7a-h(N-4-氯苯基)合成并由国家癌症研究所(NCI)针对60种不同的人类癌细胞系进行评估。吡唑啉6a,6c-h,和7a-h满足预定的阈值抑制标准，获得化合物6c和6f表现出高抗增殖活性，达到亚微摩尔GI50值从0.38到0.45μM，分别。此外，化合物7g（4-CH3）对白血病的不同癌细胞系表现出最高的细胞抑制活性，非小细胞肺，结肠,卵巢,肾,前列腺癌，LC50值范围为5.41至8.35μM，表现出比阿霉素更好的细胞毒活性。此外，测试了化合物的抗菌和抗疟原虫活性。查尔酮4c对耐甲氧西林金黄色葡萄球菌（MRSA）的活性最高，最低抑菌浓度（MIC）=2μg/mL，而吡唑啉6h对淋病奈瑟菌的MIC=8μg/mL。对于抗恶性疟原虫活性，查耳酮显示出更高的活性，EC50值为10.26至10.94μg/mL。针对恶性疟原虫的相关蛋白进行了对接研究，表现出与plasmepsinII的最小结合能。在Galleriamellonella中的体内毒性测定表明，大多数化合物是低毒或无毒的。
