Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780, Athens, Greece.
Mol Divers. 2021 Feb;25(1):307-321. doi: 10.1007/s11030-020-10082-6. Epub 2020 Apr 23.
Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups (5,7-diprenyloxy-4-methyl-coumarin, 4g) or the presence of octyloxy substituent (coumarin 4d) was found to increase the potency of compounds in breast cancer cells, but not against healthy human fibroblasts. The activity of potent compounds on breast cancer cells cultured more similarly to the conditions of the tumour microenvironment was also investigated, and increased toxicity was observed. Results suggest that tested coumarin derivatives could potentially reduce the growth of tumour mass. Moreover, their use as (combination) therapy in cancer treatment might have the potential of causing limited side effects.
香豆素具有广泛的治疗功效，但作用机制往往不明确。我们测试了一小部分 18 种香豆素衍生物对具有增殖能力的人乳腺导管癌细胞的抑制作用，并对最有效的香豆素类似物进行了进一步研究。有趣的是，发现两个prenyloxy 基团（5,7-diprenyloxy-4-methyl-coumarin，4g）的存在或辛氧基取代基（香豆素 4d）的存在会增加化合物在乳腺癌细胞中的效力，但对健康的人成纤维细胞则不然。我们还研究了活性化合物对更类似于肿瘤微环境条件培养的乳腺癌细胞的活性，结果观察到毒性增加。结果表明，测试的香豆素衍生物可能具有抑制肿瘤生长的潜力。此外，它们作为癌症治疗中的（联合）疗法，可能具有引起有限副作用的潜力。
