Ranjbari Somayeh, Behzadi Maryam, Sepehri Saghi, Dadkhah Aseman Marzieh, Jarrahpour Aliasghar, Mohkam Milad, Ghasemi Younes, Reza Akbarizadeh Amin, Kianpour Sedigheh, Atioğlu Zeliha, Özdemir Namık, Akkurt Mehmet, Masoud Nabavizadeh S, Turos Edward
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71946-84795, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Bioorg Med Chem. 2020 Apr 15;28(8):115408. doi: 10.1016/j.bmc.2020.115408. Epub 2020 Mar 4.
This article reports for the first time the synthesis of some novel β-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a-c, 9a-c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-β-lactams 8a-l, 10a-f and 12a-c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and β-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.
本文首次报道了通过亚胺7a - c、9a - c和11与取代乙酸衍生的烯酮发生[2 + 2]环加成反应合成一些新型β - 内酰胺吗啉代 - 1,3,5 - 三嗪杂化物。该反应具有完全的非对映选择性，仅生成顺式β - 内酰胺8a - l、10a - f和12a - c。通过MTT法对合成的化合物针对SW1116、MCF - 7和HepG2癌细胞系以及非癌性HEK - 293细胞系进行了活性测试。这些化合物对HepG2、MCF - 7和HEK - 293细胞均未表现出明显作用，但化合物7b、8f、8g、8l、10c和10e对SW 1116细胞表现出优异的生长抑制活性（IC＜5 μM），与阿霉素（IC = 6.9 μM）相当。通过二苯基苦味酰基肼（DPPH）法对各化合物的抗氧化潜力进行评估，结果表明7b、9a、9b和9c具有较强的自由基清除活性。紫外吸收滴定研究表明，7b、8l、8g和8f与小牛胸腺DNA（CT - DNA）有强烈相互作用，顺序为8l＞7b＞8f＞8g。总体而言，这些吗啉代 - 三嗪亚胺和β - 内酰胺中的一些化合物的体外性能表明它们在新型抗氧化剂和DNA结合治疗药物开发方面可能具有应用潜力。
