Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI₅₀ values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of β-tubulin.

较早的研究已经证实7-苯基吡咯并喹啉酮（7-PPyQ）核是靶向微管的新化学治疗药物的重要支架。对于广泛的SAR，通过鲁棒的程序合成了一系列衍生物。为了与参考3-乙基-7-PPyQ 31进行比较，改变了3位和7位的角几何形状和取代基，以探索微管蛋白秋水仙碱位点内部的相互作用。在合成的新化合物中，在白血病和实体瘤细胞系中均以21和24观察到有效的细胞毒性（低和亚纳摩尔GI ₅₀值），两者均比31强。化合物21和24都不在正常的人类淋巴细胞中，H2O3引起明显的细胞死亡，这表明这些化合物可能对癌细胞具有选择性的活性。特别地，24是A549和HeLa细胞系中凋亡的有效诱导剂。对于这两种化合物，细胞凋亡的诱导与线粒体跨膜电位的耗散和活性氧的产生有关，表明用这些化合物处理的细胞遵循细胞凋亡的内在途径。此外，免疫印迹分析表明化合物24即使在50 nM时，也会降低抗凋亡蛋白（如Bcl-2和Mcl-1）的表达。最后，对新合成的化合物的分子对接研究表明，活性吡咯并喹啉酮衍生物在β-微管蛋白的秋水仙碱位点上有很强的结合力。