Mphahlele Malose J, Khoza Tebogo A, Mabeta Peaceful
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa.
Department of Anatomy and Physiology, University of Pretoria, P/Bag X04, Pretoria 0110, South Africa.
Molecules. 2016 Dec 30;22(1):55. doi: 10.3390/molecules22010055.
Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1-pyrrolo[3,2,1-]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of . The title compounds were prepared via PdCl₂-mediated cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1-pyrrolo[3,2,1-]quinazolin-1-ones - were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except and were found to be inactive against the three cancer cell lines. Compound substituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone , on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1-pyrrolo[3,2,1-]quinazolin-1-ones - were found to be inactive against the chloroquine sensitive 3D7 strain of .
在此，我们描述了一系列新型2,3 - 二氢 - 1 - 吡咯并[3,2,1 - ]喹唑啉 - 1 - 酮的合成与评估，这些化合物针对三种人类癌细胞系进行了体外细胞毒性测试，并对氯喹敏感株3D7进行了潜在抗疟活性测试。标题化合物通过2 - 芳基 - 8 -（芳基乙炔基）- 6 - 溴 - 2,3 - 二氢喹唑啉 - 4(1) - 酮的PdCl₂介导环化反应制备。后者依次通过2 - 氨基 - 5 - 溴 - 3 - 碘苯甲酰胺与芳基乙炔的初始Sonogashira交叉偶联反应，随后中间体2 - 氨基 - 3 -（芳基乙炔基）- 5 - 溴苯甲酰胺与苯甲醛衍生物的硼酸介导环缩合反应制备。对2,3 - 二氢 - 1 - 吡咯并[3,2,1 - ]喹唑啉 - 1 - 酮针对乳腺癌（MCF - 7）、黑色素瘤（B16）和内皮瘤（sEnd.2）细胞系进行了潜在体外细胞毒性评估。除[具体化合物]和[具体化合物]外，所有化合物对这三种癌细胞系均无活性。在3 - 和5 - 位被4 - 甲氧基苯基和4 - 氟苯基取代的化合物对这三种癌细胞系表现出显著的细胞毒性。另一方面，在吡咯并喹唑啉酮[具体化合物]的3 - 和5 - 位存在苯基和3 - 氯苯基导致对血管肿瘤内皮细胞（sEnd.2）有显著细胞毒性，但对黑色素瘤（B16）和乳腺癌（MCF - 7）细胞的活性降低，除了在较高浓度时。发现2,3 - 二氢 - 1 - 吡咯并[3,2,1 - ]喹唑啉 - 1 - 酮对氯喹敏感的3D7株[疟原虫]无活性。
