Semenova Marina N, Melik-Nubarov Nikolay S, Semenov Victor V
N.K. Koltzov Institute of Developmental Biology RAS, 26 Vavilov Street, 119334 Moscow, Russia.
Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory, 1/11B, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Sep 28;24(19):14695. doi: 10.3390/ijms241914695.
In screening, the dilution of DMSO stock solution of a lipophilic molecule with an assay medium often causes compound precipitation. To overcome the issue, the application of Pluronics as cosolvents was examined using a phenotypic sea urchin embryo assay that allows for the quick and facile evaluation of the antiproliferative effect together with systemic toxicity. Maximum tolerated concentration values for Pluronics L121, P123, and F127 were 1.4 μM, 8.6 μM, and 39.7 μM, respectively, and correlated directly with their hydrophilicity. Pluronics L121 and P123 suppressed cleavage and blastomeres retained the round shape, unlike hydrophilic Pluronic F127, which induced fertilization envelope creasing and embryo deformation that could be associated with the interaction of hydrophilic PEO units with mucopolysaccharides at the surface of sea urchin embryos. The toxicity of P123, but not of L121 and F127, was temperature-dependent and markedly increased at lower temperatures. CMC values obtained at different temperatures confirmed that the toxic effect of P123 was associated with both unimers and micelles, whereas F127 toxicity was related mainly to micelles. Evaluation using phenotypic sea urchin embryo assay revealed that potent microtubule destabilizers, namely albendazole, diarylisoxazole, and two chalcones, retained antimitotic activity after the dilution of their DMSO or 2-pyrrolidone stock solutions with 1.25% / Pluronic P123 or 5% / Pluronic F127. It was suggested that Pluronic P123 and Pluronic F127 could be used as cosolvents to improve the solubility of lipophilic molecules in aqueous medium.
在筛选过程中，用测定培养基稀释亲脂性分子的二甲基亚砜储备溶液常常会导致化合物沉淀。为解决这一问题，使用海胆胚胎表型分析方法研究了普朗尼克类作为助溶剂的应用，该分析方法能够快速简便地评估抗增殖作用以及全身毒性。普朗尼克L121、P123和F127的最大耐受浓度值分别为1.4 μM、8.6 μM和39.7 μM，且与它们的亲水性直接相关。与亲水性的普朗尼克F127不同，普朗尼克L121和P123抑制卵裂，卵裂球保持圆形，而F127会诱导受精膜起皱和胚胎变形，这可能与亲水性的聚环氧乙烷单元与海胆胚胎表面的粘多糖相互作用有关。P123的毒性具有温度依赖性，而L121和F127则不具有，且在较低温度下显著增加。在不同温度下获得的临界胶束浓度值证实，P123的毒性与单体和胶束均有关，而F127的毒性主要与胶束有关。使用海胆胚胎表型分析进行的评估表明，强效微管去稳定剂，即阿苯达唑、二芳基异恶唑和两种查耳酮，在用1.25%/普朗尼克P123或5%/普朗尼克F127稀释其二甲基亚砜或2-吡咯烷酮储备溶液后仍保留抗有丝分裂活性。有人提出，普朗尼克P123和普朗尼克F127可用作助溶剂，以提高亲脂性分子在水性介质中的溶解度。
