源自植物和微生物的天然化合物及其组合目前正在作为可能治疗多种疾病，包括癌症的方法进行研究。Hypericum perforatum L.中的光动力活性色素hypericin和Streptomyces parvulus中的法尼酰转移酶抑制剂manumycin A属于可能适用于临床实践的化学物质。在本研究中，我们评估了这些化合物及其组合在细胞外和细胞系统中的作用分子机制，并考虑了其潜在的细胞毒性(通过尝试蓝色排除试验)、遗传毒性(通过DNA拓扑和彗星试验)和突变原性(通过细菌反转突变试验)。我们的结果未显示出受测试化合物及其组合的细胞毒性或突变原性。关于遗传毒性的潜在风险，没有在细胞外系统中检测到质粒DNA的损伤。另一方面，通过彗星试验分析，光激活的hypericin和manumycin A能够引起人淋巴细胞的原发性DNA损伤。使用SynergyFinder软件分析和从彗星试验获得的实验数据估计了这两种代谢物之间的可能对抗作用。我们的发现表明，在细胞系统中，不仅物质的存在，而且其比例对于组合治疗的效果也起着重要的作用。版权所有 © 2023 Elsevier B.V.

Natural compounds originated from plants and microorganisms and their combinations are currently being investigated as a possible treatment for several diseases including cancer. Hypericin (photodynamically-active pigment from Hypericum perforatum L.) and manumycin A (inhibitor of farnesyltransferase from Streptomyces parvulus) belong to the chemicals potentially applicable in clinical practice. In this study we evaluated potential cytotoxic (via trypan blue exclusion test), genotoxic (via DNA-topology and comet assays), and mutagenic effects (via bacterial reverse mutation test) of these compounds and their combinations considering the molecular mechanism of their action in cell-free and cellular systems. Our results did not reveal neither cytotoxic nor mutagenic activities of tested compounds and their combinations. Regarding the genotoxic potential, no damage of plasmid DNA in cell-free system was detected. On the other hand, photoactivated hypericin and manumycin A were able to induce primary DNA damage in human lymphocytes analyzed by comet assay. The possible antagonistic interactions between these two metabolites were estimated using SynergyFinder software analysis and experimental data obtained from comet assay. Our findings indicate that not only the presence of substances, but also their ratio plays an important role in resulting effects of the combined treatment in cellular system.Copyright © 2023 Elsevier B.V. All rights reserved.