PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Solubilized Formulations of Triphenylphosphine Derivatives of Allylbenzenes and Their Potential as Individual Antitumor Agents or Adjuvants to Paclitaxel
Zlotnikov, I.D.; Krylov, S.S.; Semenova, M.N.; Semenov, V.V.; Kudryashova, E.V. Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations. Pharmaceuticals2023, 16, 1651.
Zlotnikov, I.D.; Krylov, S.S.; Semenova, M.N.; Semenov, V.V.; Kudryashova, E.V. Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations. Pharmaceuticals 2023, 16, 1651.
Zlotnikov, I.D.; Krylov, S.S.; Semenova, M.N.; Semenov, V.V.; Kudryashova, E.V. Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations. Pharmaceuticals2023, 16, 1651.
Zlotnikov, I.D.; Krylov, S.S.; Semenova, M.N.; Semenov, V.V.; Kudryashova, E.V. Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations. Pharmaceuticals 2023, 16, 1651.
Abstract
Allylbenzenes (apiol, dillapiol, myristicin and allyltetramethoxybenzene) are individual components of plant essential oils that demonstrate antitumor activity, as well as enhancing effect on cytotoxic drugs such as paclitaxel, doxorubicin, cisplatin, etc. Triphenylphosphine (PPh3) derivatives of allylbenzenes are 2-3 orders of magnitude more potent than allylbenzenes in terms of IC50. Inhibition of efflux pumps has been reported for allylbenzenes, and PPh3 moiety is deemed to be responsible for preferential mitochondrial accumulation and depolarization of mitochondrial membranes. However, due to poor solubility the practical use of these substances has never been an option. Cyclodextrin-based (CD) molecular containers suggested here provided solubilization of allylbenzenes and its PPh3-derivatives. So, in this study we have observed an increase antitumor activity of paclitaxel in the presence of PPh3-derivatives adjuvants by an order of magnitude (in terms of IC50) against adenocarcinomic human alveolar basal epithelial cells A549. At the same time, they are quite powerful cytostatics themselves against A549 cells. On the other hand, the cytotoxic formulations developed show pronounced selectivity of the antiproliferation activity: high against tumor cells line (A549) and low toxicity of these composition was demonstrated on normal cells HEK293T, red blood cells, and sea urchin embryos (a model close to the human genome). On non-cancer HEK293T cells, it was shown that PPh3-derivatives of allylbenzenes at a concentration of 100 µM cause the death of about 20% of cells, while on A549 cancer cells, 85% of cells die. PPh3 derivatives of allylbenzenes, when solubilized in CD molecular containers, show remarkable potential as adjuvants to some of the widely used cytotoxic drugs.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
