Rational Design 2-Hydroxypropylphosphonium Salts as Cancer Cell Mitochondria-Targeted Vectors: Synthesis,Structure, and Biological Properties |
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| Authors: | Vladimir F Mironov Andrey V Nemtarev Olga V Tsepaeva Mudaris N Dimukhametov Igor A Litvinov Alexandra D Voloshina Tatiana N Pashirova Eugenii A Titov Anna P Lyubina Syumbelya K Amerhanova Aidar T Gubaidullin Daut R Islamov |
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| Institution: | 1.Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov St., 420088 Kazan, Russia; (A.V.N.); (O.V.T.); (M.N.D.); (I.A.L.); (A.D.V.); (T.N.P.); (A.P.L.); (S.K.A.); (A.T.G.); (D.R.I.);2.Alexander Butlerov Institute of Chemistry, Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russia; |
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| Abstract: | It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride etherate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolecular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailability and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells. |
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| Keywords: | phosphonium salt P– C bond formation oxirane glycidyl ether triphenylphosphine addition reaction nucleophilic substitution |
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