Water-Soluble Salts Based on Benzofuroxan Derivatives-Synthesis and Biological Activity

被引:4
作者
Chugunova, Elena [1 ]
Matveeva, Victoria [1 ]
Tulesinova, Alena [2 ]
Iskanderov, Emil [3 ]
Akylbekov, Nurgali [4 ]
Dobrynin, Alexey [1 ]
Khamatgalimov, Ayrat [1 ]
Appazov, Nurbol [4 ,5 ]
Boltayeva, Lyazat [6 ,7 ]
Duisembekov, Bakhytzhan [6 ,7 ]
Zhanakov, Mukhtar [8 ]
Aleksandrova, Yulia [1 ,9 ]
Sashenkova, Tatyana [10 ]
Klimanova, Elena [10 ]
Allayarova, Ugulzhan [10 ]
Balakina, Anastasia [10 ]
Mishchenko, Denis [10 ,11 ]
Burilov, Alexander [1 ]
Neganova, Margarita [1 ,9 ]
机构
[1] Russian Acad Sci, Arbuzov Inst Organ & Phys Chem, FRC Kazan Sci Ctr, Kazan 420088, Russia
[2] Kazan Natl Res Technol Univ, Kazan 420015, Russia
[3] Kazan Fed Univ, Kazan 420008, Russia
[4] Korkyt Ata Kyzylorda Univ, Lab Engn Profile Phys & Chem Methods Anal, Kyzylorda 120014, Kazakhstan
[5] I Zhakhaev Kazakh Sci Res Inst Rice Growing, Kyzylorda 120008, Kazakhstan
[6] Quarantine Named Zhazken Zhiembayev LLP, Alma Ata, Kazakhstan
[7] Kazakh Sci Res Inst Plant Protect, Alma Ata, Kazakhstan
[8] L N Gumilyov Eurasian Natl Univ, Astana 010008, Kazakhstan
[9] Russian Acad Sci, Fed Res Ctr Problems Chem Phys & Med Chem, Inst Physiol Act Cpds, Chernogolovka 142432, Russia
[10] RAS, Fed Res Ctr Problems Chem Phys & Med Chem, Chernogolovka 142432, Russia
[11] MV Lomonosov MSU, Fac Fundamental Phys Chem Engn, Moscow 119991, Russia
基金
俄罗斯科学基金会;
关键词
benzofuroxan; water-soluble salt; cancer; glycolysis; phytopathological analyses of agricultural crops; growth stimulators and regulators; acute toxicity; MOLECULAR-ORBITAL METHODS; GAUSSIAN-TYPE BASIS; ORAL DELIVERY; FUROXANS; CHEMISTRY;
D O I
10.3390/ijms232314902
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of novel water-soluble salts of benzofuroxans was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan with various amines. The salts obtained showed good effectiveness of the pre-sowing treatment of seeds of agricultural crops at concentrations of 20-40 mmol. In some cases, the seed treatment with salts leads not only to improved seed germination, but also to the suppression of microflora growth. Additionally, their anti-cancer activityin vitrohas been researched. The compounds with morpholine fragments or a fragment of N-dimethylpropylamine, demonstrated the highest cytotoxic activity, which is in good correlation with the ability to inhibit the glycolysis process in tumor cells. Two compounds 4e and 4g were selected for further experiments using laboratory animals. It was found that the lethal dose of 50% (LD50) is 22.0 +/- 1.33 mg/kg for 4e and 13.75 +/- 1.73 mg/kg for 4g, i.e., compound 4e is two times less toxic than 4g, according to the mouse model in vivo. It was shown that the studied compounds exhibit antileukemia activity after a single intraperitoneal injection at doses from 1.25 to 5 mg/kg, as a result of which the average lifespan of animals with a P388 murine leukemia tumor increases from 20 to 28%. Thus, the water-soluble salts of benzofuroxans can be considered as promisingcandidates for further development, both as anti-cancer agents and as stimulants for seed germination and regulators of microflora crop growth.
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页数:21
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