Synthesis and preliminary cytotoxicity evaluation of water soluble pentacyclic triterpenoid phosphonates

被引：0

作者：

Luginina, Jevgenija ^{[1
]}

Kroskins, Vladislavs ^{[1
]}

Lacis, Rihards ^{[1
]}

Fedorovska, Elza ^{[1
]}

Demir, Oznur ^{[2
,3
]}

Dubnika, Arita ^{[2
,3
]}

Loca, Dagnija ^{[2
,3
]}

Turks, Maris ^{[1
]}

机构：

[1] Riga Tech Univ, Inst Chem & Chem Technol, Fac Nat Sci & Technol, 3 P Valdena St, LV-1048 Riga, Latvia

[2] Riga Tech Univ, Inst Biomat & Bioengn, Fac Nat Sci & Technol, 3 Pulka St, LV-1048 Riga, Latvia

[3] Riga Tech Univ, Balt Biomat Ctr Excellence, Riga, Latvia

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

Pentacyclic triterpenoids; Phosphonates; Cytotoxicity; Aqueous solubility; OLEANOLIC ACID; BETULINIC ACID; URSOLIC ACID; DERIVATIVES SYNTHESIS; CELL-CYCLE; PRODRUGS; MITOCHONDRIA; INHIBITION; ACTIVATION; PHOSPHATE;

D O I：

10.1038/s41598-024-76816-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synthesis, solubility and cytotoxicity evaluation of anionic phosphonates derived from betulin, betulinic acid, oleanolic acid and ursolic acid is reported. Phosphonate moieties were successfully installed at terpenoid C28 by carboxylic acid deprotonation/alkylation sequence using (dimethoxyphosphoryl)methyl trifluoromethanesulfonate as alkylation reagent. Also, betulin-derived and ether-linked bis-phosphonate is obtained and characterized. After demethylation in the presence of TMSI the resulting phosphonic acids were transformed into their disodium salts. All target compounds display excellent water solubility, which was determined by qNMR in D2O. Cytotoxicity tests were performed in different concentrations of each compound (10-50 mu M) against human osteosarcoma cell line MG-63 and osteoblast precursor cell line MC3T3-E1. Improved aqueous solubility and low cytotoxicity profile of the newly designed triterpenoid phosphonates reveal high potential for various medicinal chemistry and pharmacological applications in the future.

引用

页数：15

共 81 条

[1]

ALY O A, 1982, Environment International, V7, P373, DOI 10.1016/0160-4120(82)90152-0

[2] Betulin and its derivatives as novel compounds with different pharmacological effects [J].

Amiri, Shayan ;

Dastghaib, Sanaz ;

Ahmadi, Mazaher ;

Mehrbod, Parvaneh ;

Khadem, Forough ;

Behrouj, Hamid ;

Aghanoori, Mohamad-Reza ;

Machaj, Filip ;

Ghamsari, Mahdi ;

Rosik, Jakub ;

Hudecki, Andrzej ;

Afkhami, Abbas ;

Hashemi, Mohammad ;

Los, Marek J. ;

Mokarram, Pooneh ;

Madrakian, Tayyebeh ;

Ghavami, Saeid .

BIOTECHNOLOGY ADVANCES, 2020, 38

[3] Self-assembly of sodium and potassium betulinates into hydro- and organo-gels: entrapment and removal studies of fluorophores and synthesis of gel-gold nanoparticle hybrid materials [J].

Bag, Braja Gopal ;

Dash, Shib Shankar .

RSC ADVANCES, 2016, 6 (21) :17290-17296

[4] Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma [J].

Basu, Aalok ;

Namporn, Thanaphon ;

Ruenraroengsak, Pakatip .

PHARMACEUTICS, 2023, 15 (06)

[5] Application of Relay C-H Oxidation Logic to Polyhydroxylated Oleanane Triterpenoids [J].

Berger, Martin ;

Knittl-Frank, Christian ;

Bauer, Sophie ;

Winter, Georg ;

Maulide, Nuno .

CHEM, 2020, 6 (05) :1183-1189

[6] Synthesis, Structure and Cytotoxic Activity of New Acetylenic Derivatives of Betulin [J].

Boryczka, Stanislaw ;

Bebenek, Ewa ;

Wietrzyk, Joanna ;

Kempinska, Katarzyna ;

Jastrzebska, Maria ;

Kusz, Joachim ;

Nowak, Maria .

MOLECULES, 2013, 18 (04) :4526-4543

[7] Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates [J].

Bureeva, Svetlana ;

Andia-Pravdivy, Julian ;

Symon, Andrey ;

Bichucher, Anna ;

Moskaleva, Vera ;

Popenko, Vladimir ;

Shpak, Alexey ;

Shvets, Vitaly ;

Kozlov, Leonid ;

Kaplun, Alexander .

BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (10) :3489-3498

[8] Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges [J].

Cerreia Vioglio, Paolo ;

Chierotti, Michele R. ;

Gobetto, Roberto .

ADVANCED DRUG DELIVERY REVIEWS, 2017, 117 :86-110

[9] Antiproliferative and Cytotoxic Properties of Propynoyl Betulin Derivatives against Human Ovarian Cancer Cells: In Vitro Studies [J].

Chodurek, Ewa ;

Orchel, Arkadiusz ;

Gwiazdon, Pawel ;

Kaps, Anna ;

Paduszynski, Piotr ;

Jaworska-Kik, Marzena ;

Chrobak, Elwira ;

Bebenek, Ewa ;

Boryczka, Stanislaw ;

Kasperczyk, Janusz ;

Nakayama, Kentaro .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (22)

[10] Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin [J].

Chrobak, Elwira ;

Jastrzebska, Maria ;

Bebenek, Ewa ;

Kadela-Tomanek, Monika ;

Marciniec, Krzysztof ;

Latocha, Malgorzata ;

Wrzalik, Roman ;

Kusz, Joachim ;

Boryczka, Stanislaw .

MOLECULES, 2021, 26 (03)

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