МОДЕЛЮВАННЯ ТА СИНТЕЗ НОВИХ ГОМО- ТА ГЕТЕРОМЕТАЛІЧНИХ КООРДИНАЦІЙНИХ СПОЛУК ГЕРМАНІЮ(IV) ДЛЯ СТВОРЕННЯ НИЗЬКОТОКСИЧНИХ ПРЕПАРАТІВ ШИРОКОЇ ТЕРАПЕВТИЧНОЇ ДІЇ

I. I. Seifullina, E. E. Martsinko, E. V. Afanasenko

Анотація


В оглядовій статті розглянуті вперше синтезовані на кафедрі загальної хімії та полімерів ОНУ ім. І.І. Мечникова гомо- і гетерометалічні координаційні сполуки германію(IV) з біолігандами (нікотинова, лимонна, винна, 1-гідроксіетилідендифосфонова кислоти, нікотінамід) – природними метаболітами організму людини, широко застосовуваними у медицині. Охарактеризовано вплив сполук германію(IV) на процеси життєдіяльності тварин і людини, встановлена їх антигіпоксична, імуностимулююча, кардіотропна, антиоксидантна, нейротропна, протизапальна та ін. активність. Показані перспективи подальшого синтезу та вивчення координаційних сполук германію(IV) з біологічно активними лігандами.


Ключові слова


германій, координаційні сполуки, біоліганди, біологічна активність, терапевтична дія

Повний текст:

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Посилання


Marczynski B. Carcinogenesis as the result of the deficiency of some essential trace elements. Medical Hypotheses, 1988, vol. 4, no 4, pp. 239-249. http://dx.doi.org/10.1016/0306-9877(88)90127-2

http://www.germaniumsesquioxide.com

Seifullina I.I., Martsinko E.E., Aleksandrov G.G. Sergienko V.S. Synthesis, Properties, and Structure of Polynuclear Hydroxyethylidene-1,1-diphosphonatogermanates; Crystal and Molecular Structure of Two Complexes on the Basis of These Compounds. Rus. J. Inorg. Chem, 2004, vol. 49, no 6, pp. 844-852.

Seifullina I.I., Pesaroglo A.G., Minacheva L.Kh., Martsinko E.E., Sergienko V.S. Bis(citrato)germinate Complexes with Organic Cations: Crystal Structure of (HNic)2[Ge(HCit)2]·3H2O. Rus. J. Inorg. Chem, 2006, vol. 51, no 12, pp. 1892-1899. http://dx.doi.org/10.1134/s0036023606120096

Seifullina I.I., Ilyukhin A.B., Martsinko E.E., Sergienko V.S., Chebanenko E.A. Products of Reaction between Bis(citrate)hydroxogermanic Acid and Organic Molecules. Molecular and Crystal Structure of (HNad)2[Ge(HCit)2] 4H2O. Rus. J. Inorg. Chem., 2015, vol. 60, no 1, pp. 33-37. http://dx.doi.org/10.1134/s0036023615010143

Martsinko E.E., Seifullina I.I., Minacheva L.Kh., Pesaroglo A.G., Sergienko V.S. Synthesis, Properties, and Molecular and Crystal Structure of Diantipyrylmethanium Bis( -Tartrato)dihydroxydigermanate(IV) Tetrahydrate (HDam)2[Ge2( -L)2(OH)2] · 4H2O. Rus. J. Inorg. Chem, 2008, vol. 53, no 11, pp. 1694-1702. http://dx.doi.org/10.1134/s0036023608110053

Pesaroglo A.G., Martsinko E.E., Minacheva L.Kh., Seifullina I.I., Sergienko V.S. The Coordination Polymer Triaquabarium- -bis(citrato)germanate Trihydrate: Synthesis, Properties, Molecular and Crystal Structure of {[Ge( -HCit)2Ba(H2O)3]·3H2O}n. Rus. J. Inorg. Chem., 2010, vol. 55, no 9, pp. 1366-1372. http://dx.doi.org/10.1134/s0036023610090068

Martsinko E.E., Minacheva L.Kh., Pesaroglo A.G., Seifullina I.I., Churakov A.V., Sergienko V.S. Bis(citrato) germanates of Bivalent 3d Metals (Fe, Co, Ni, Cu, Zn): Crystal and Molecular Structure of [Fe(H2O)6] [Ge(HCit)2]·4H2O. Rus. J. Inorg. Chem., 2011, vol. 56, no 8, pp. 1243-1249. http://dx.doi.org/10.1134/s0036023611080171

Martsinko E.E., Minacheva L.Kh., Chebanenko E.A., Seifullina I.I., Sergienko V.S., Churakov A.V. The Conditions of Formation of Heterometallic Complexes in the GeCl4 (SnCl4)–Citric Acid–M(CH3COO)2–H2O Systems. The Crystal and Molecular Structures of [M(H2O)6][Ge(HCit)2] 4H2O (M = Mg, Mn, Co, Cu, Zn) and [M(H2O)6][Sn(HCit)2] 4H2O (M = Mg, Co, Ni). Rus. J. Inorg. Chem., 2013, vol. 58, no 5, pp. 515-522. http://dx.doi.org/10.1134/s003602361305015x

Martsinko E.E., Minacheva L.Kh., Chebanenko E.A., Ilyukhin A.B., Seifullina I.I., Sergienko V.S. Ammonium and Potassium Citratogermanates(IV): Synthesis, Chemical Compositions, and Structures. The Crystal Structures of (NH4)[Ge(OH)(H2Cit)2]·H2O and K4[Ge(HCit)2(H2Cit)]·3H2O. Rus. J. Coord. Chem., 2013, vol. 39, no 9, pp. 629-635. http://dx.doi.org/10.1134/s1070328413090054

Minacheva L.Kh., Seifullina I.I., Ilyukhin A.B., Martsinko E.E., Sergienko V.S., Chebanenko E.A., Churakov A.V. Strategy for the Synthesis of Di- and Polymer Tartratogermanates with Single-Charge Cations. Crystal Structures of K2[Ge2(OH)2( -Tart)2]·4.5H2O and (NH4)2n[Ge2( -O)( -Tart)2]n·nMeCN·nH2O. Rus. J. Coord. Chem., 2013, vol. 39, no 11, pp. 751-757. http://dx.doi.org/10.1134/s1070328413110043

Martsinko E.E., Pesaroglo A.G., Minacheva L.Kh., Seifullina I.I. et al. Synthesis, Properties, and Molecular and Crystal Structure of Hexaaquacopper(IV) Bis(diaquacuprato-μ3-trihydroxyglutarato)germanate(IV) Dihydrate [Cu(H2O)6][Ge(μ3-Thgl)2{Cu(H2O)2}2]2H2O Rus. J. Inorg. Chem., 2011, vol. 56, no 2, pp. 190-196. http://dx.doi.org/10.1134/s0036023611020197

Martsinko E.E., Minacheva L.Kh., Seifullina I.I. et al. Heteronuclear Alkali Metal bis(μ_Trihydroxoglutarato) dihydroxodigermanates(IV). The Crystal and Molecular Structure of К4[Ge2(m-Thgl)2(OH)2]∙4Н2О. Rus. J. Inorg. Chem., 2012, vol. 57, no 3, pp. 343-349. http://dx.doi.org/10.1134/s0036023612030199

Martsinko E.E., Pesaroglo A.G., Minacheva L.Kh., Seifullina I.I. et al. Synthesis and Characterization of Cobalt(II) and Manganese(II) Xylaratogermanates: The Molecular and Crystal Structures of the [M(H2O)6][Ge(μ3-L)2{M(H2O)2}2]*4H2O*nCH3CN Complexes (M = Co, n = 0; M = Mn, n = 1).Rus. J. Inorg. Chem., 2013, vol. 58, no 2, pp. 152-159. http://dx.doi.org/10.1134/s0036023613020174

Pat. 19965 Ukraine, (51) МПК (2006), А61К 31/19 (2006.01), А61К 33/12 (2006.01), А61К 33/24. Magnesium-oxyethylidendiphosphonate germanate which is characterized by vasotropic action / V.V. Godovan, V.Y. Kresyun, I.I. Seifullina. – Bull. №1. 15.01.2007.

Pat. 20658 Ukraine, (51) МПК (2007), А61К 31/19 (2007.01), А61К 33/00. Biologically active antiunrhythmical substance „germacord” / V.V. Godovan, V.Y. Kresyun, I.I. Seifullina. – Bull. №2. 15.02.2007.

Kresyun V.Y., Seifullina I.Y., Vidavska G.G., Shemonayeva K.F. Perspectives of new Oxyethylidendiphosphonate acid-based pharmaceuticals creation. Medical Chemistry, 2004, vol. 6, no 3, pp.133-138.

Voloshenkov D.B. Neurotropic effects of coordination compounds on the base of germanium oxyethylendiphosphonate with nicotinic acid, nicotinamide and magnesium. – A manuscript. Thesis for a scientific degree of kandidate of medical sciences in speciality 14.03.05 – pharmacology. – Odessa State Medical University Ministry of Health Care of Ukraine. Odessa, 2008. pp 157.

Pat. 36684 Ukraine, (51) МПК (2008), А61К31/045, А61К33/00. Method of detoxication of organism at endtoxicosis of posttraumatic origin by means of coordination compound on the base of germanium, magnesium and oxyethylidenediphosphononate acid / V.D. Lukjanchuk, I.I. Seifullina, N.V. Risukhina, E.E. Martsinko. – Bull. №21. 10.11.2008.

Lukyanchuk V.D., Seifullina I.I., Risukhina N.V. EPR-spectrometric analysis of protective action of coordination compound of germanium with magnesium and oxyethylidendiphosphonic acid in conditions of crush-syndrome. J. Academy of Medical Sciences of Ukraine, 2008, vol. 14, no 3, pp. 593-601.

Pat. 613475А Ukraine, (19)UA, (51) МПК (2003), А61К31/455, А61К33/00. Coordination compounds of germanium with nicotinic acid having antihypoxant activity / I.I. Seifullina, V.D. Lukjanchuk, O.D. Nemyalyk. – Bull. №17.11.2003.

Pat. 22954 Ukraine, (19)UA, (51) МПК (2006), G01N 33/576, А61К 39/29. Method of pharmaceutical correction of toxic medicinal hepatitis / V.D. Lukjanchuk, M.A. Vnukova, I.I. Seifullina, O.O. Shpulina, V.N. Тkachenko. – Bull. №5. 25.04.2007.

Godovan V.V., Kresyun V.Y., Seifullina I.Y. Comparative Pharmacological Activity of New Biologically Active Substances — Derivatives of Diphosphonate Acids. Integrative Anthropology. International Medical and Philosophical Magazine, 2007, no 2(10), pp.13-17.

Seifullina I.I., Martsinko E.E., Spivak N. Ya., Zholobak N.M. The polymolecular aggregates of nicotinic acid, nicotinamide, pyracetam with oxyethylidenediphosphononatohydroxygermanium acid and their interferonogenic activities. Abstr. Rep. XX Ukr. Conf. Organic Chemistry. Odessa, 2004, pp. 443.

Pat. 66392 Ukraine, (51) МПК (2011.01), А61P 1/16 (2006.01), А61К 31/30 (2006.01), А61K 9/14 (2006.01). Medgerm is biologically active hepatoprotective agent / O.L. Tymchishin, V.V. Godovan, V.Y. Kresyun, I.I. Seifullina, E.E. Martsinko. – Bull. №24. 26.11.2011.

Pat. 20555 Ukraine, (19)UA, (51) МПК (2006), А61К 35/30. The method of Pharmacological correction of a craniocereberal trauma / Lukyanchuk V.D., Seyfullina І.I., Vysotsky A.A., Martsinko E.E., Pesaroglo O.G. – Bull. №1. 15.01.2007.

Pat. 71812 Ukraine, МПК (2012.01) А61Р 9/00 А61К 33/00. Potassium bis(citrato)germanate (IV), that shows the antiischemic activity / V.D. Lukyanchuk, І.O. Zhitina, I.I. Seifullina, E.E. Martsinko. – Bull. № 14.


Пристатейна бібліографія ГОСТ


1. Marczynski B. Carcinogenesis as the result of the deficiency of some essential trace elements // Medical Hypotheses.– 1988. – Vol. 4, N4. – P. 239-249. http://dx.doi.org/10.1016/0306-9877(88)90127-2

 

2. http://www.germaniumsesquioxide.com

 

3. Seifullina I.I., Martsinko E.E., Aleksandrov G.G. Sergienko V.S., Synthesis, Properties, and Structure of Polynuclear Hydroxyethylidene-1,1-diphosphonatogermanates; Crystal and Molecular Structure of Two Complexes on the Basis of These Compounds // Rus. J. Inorg. Chem. – 2004. – V. 49, № 6. – P. 844-852.

 

4. Seifullina I.I., Pesaroglo A.G., Minacheva L.Kh., Martsinko E.E., Sergienko V.S. Bis(citrato)germinate Complexes with Organic Cations: Crystal Structure of (HNic)2[Ge(HCit)2]·3H2O // Rus. J. Inorg. Chem. – 2006. – V. 51, № 12. – P. 1892-1899. http://dx.doi.org/10.1134/s0036023606120096

 

5. Seifullina I.I., Ilyukhin A.B., Martsinko E.E., Sergienko V.S., Chebanenko E.A. Products of Reaction between Bis(citrate)hydroxogermanic Acid and Organic Molecules. Molecular and Crystal Structure of (HNad)2[Ge(HCit)2] 4H2O // Rus. J. Inorg. Chem. – 2015. – V. 60, № 1. – P. 33-37. http://dx.doi.org/10.1134/s0036023615010143

 

6. Martsinko E.E., Seifullina I.I., Minacheva L.Kh., Pesaroglo A.G., Sergienko V.S. Synthesis, Properties, and Molecular and Crystal Structure of Diantipyrylmethanium Bis( -Tartrato)dihydroxydigermanate(IV) Tetrahydrate (HDam)2[Ge2( -L)2(OH)2] · 4H2O // Rus. J. Inorg. Chem. – 2008. – V. 53, № 11. – P. 1694-1702. http://dx.doi.org/10.1134/s0036023608110053

 

7. Pesaroglo A.G., Martsinko E.E., Minacheva L.Kh., Seifullina I.I., Sergienko V.S. The Coordination Polymer Triaquabarium- -bis(citrato)germanate Trihydrate: Synthesis, Properties, Molecular and Crystal Structure of {[Ge( -HCit)2Ba(H2O)3]·3H2O}n // Rus. J. Inorg. Chem. – 2010. – V. 55, № 9. – 1366-1372. http://dx.doi.org/10.1134/s0036023610090068

 

8. Martsinko E.E., Minacheva L.Kh., Pesaroglo A.G., Seifullina I.I., Churakov A.V., Sergienko V.S. Bis(citrato)germanates of Bivalent 3d Metals (Fe, Co, Ni, Cu, Zn): Crystal and Molecular Structure of [Fe(H2O)6][Ge(HCit)2]·4H2O // Rus. J. Inorg. Chem. – 2011. – V. 56, № 8. – 1243-1249. http://dx.doi.org/10.1134/s0036023611080171

 

9. Martsinko E.E., Minacheva L.Kh., Chebanenko E.A., Seifullina I.I., Sergienko V.S., Churakov A.V. The Conditions of Formation of Heterometallic Complexes in the GeCl4 (SnCl4)–Citric Acid–M(CH3COO)2–H2O Systems. The Crystal and Molecular Structures of [M(H2O)6][Ge(HCit)2] 4H2O (M = Mg, Mn, Co, Cu, Zn) and [M(H2O)6][Sn(HCit)2] 4H2O (M = Mg, Co, Ni) // Rus. J. Inorg. Chem. – 2013. – V. 58, № 5. – 515-522. http://dx.doi.org/10.1134/s003602361305015x

 

10. Martsinko E.E., Minacheva L.Kh., Chebanenko E.A., Ilyukhin A.B., Seifullina I.I., Sergienko V.S. Ammonium and Potassium Citratogermanates(IV): Synthesis, Chemical Compositions, and Structures. The Crystal Structures of (NH4)[Ge(OH)(H2Cit)2]·H2O and K4[Ge(HCit)2(H2Cit)]·3H2O // Rus. J. Coord. Chem. – 2013. – V. 39, № 9. – 629-635. http://dx.doi.org/10.1134/s1070328413090054

 

11. Minacheva L.Kh., Seifullina I.I., Ilyukhin A.B., Martsinko E.E., Sergienko V.S., Chebanenko E.A., Churakov A.V. Strategy for the Synthesis of Di- and Polymer Tartratogermanates with Single-Charge Cations. Crystal Structures of K2[Ge2(OH)2( -Tart)2]·4.5H2O and (NH4)2n[Ge2( -O)( -Tart)2]n·nMeCN·nH2O // Rus. J. Coord. Chem. – 2013. – V. 39, № 11. – 751-757. http://dx.doi.org/10.1134/s1070328413110043

 

12. Martsinko E.E., Pesaroglo A.G., Minacheva L.Kh., Seifullina I.I. et al. Synthesis, Properties, and Molecular and Crystal Structure of Hexaaquacopper(IV) Bis(diaquacuprato-μ3-trihydroxyglutarato)germanate(IV) Dihydrate [Cu(H2O)6][Ge(μ3-Thgl)2{Cu(H2O)2}2]2H2O // Rus. J. Inorg. Chem. – 2011. – V. 56, № 2. – P. 190-196. http://dx.doi.org/10.1134/s0036023611020197

 

13. Martsinko E.E., Minacheva L.Kh., Seifullina I.I. et al. Heteronuclear Alkali Metal bis(μ-Trihydroxoglutarato) dihydroxodigermanates(IV). The Crystal and Molecular Structure of К4[Ge2(m-Thgl)2(OH)2]∙4Н2О // Rus. J. Inorg. Chem. – 2012. – V. 57, № 3. – P. 343-349. http://dx.doi.org/10.1134/s0036023612030199

 

14. Martsinko E.E., Pesaroglo A.G., Minacheva L.Kh., Seifullina I.I. et al. Synthesis and Characterization of Cobalt(II) and Manganese(II) Xylaratogermanates: The Molecular and Crystal Structures of the [M(H2O)6] [Ge(μ3-L)2{M(H2O)2}2]*4H2O*nCH3CN Complexes (M = Co, n = 0; M = Mn, n = 1) // Rus. J. Inorg. Chem. –2013. – V. 58, № 2. – P. 152-159. http://dx.doi.org/10.1134/s0036023613020174

 

15. Pat. 19965 Ukraine, (51) МПК (2006), А61К 31/19 (2006.01), А61К 33/12 (2006.01), А61К 33/24. Magnesium-oxyethylidendiphosphonate germanate which is characterized by vasotropic action / V.V. Godovan, V.Y. Kresyun, I.I. Seifullina. – Bull. №1. 15.01.2007.

 

16. Pat. 20658 Ukraine, (51) МПК (2007), А61К 31/19 (2007.01), А61К 33/00. Biologically active antiarrhythmical substance „germacord” / V.V. Godovan, V.Y. Kresyun, I.I. Seifullina. – Bull. №2. 15.02.2007.

 

17. Kresyun V.Y., Seifullina I.Y., Vidavska G.G., Shemonayeva K.F. Perspectives of new Oxyethylidendiphosphonate acid-based pharmaceutical preparations // Medical Chemistry. – 2004. – Vol.6, No 3. – P.133-138.

 

18. Voloshenkov D.B. Neurotropic effects of coordination compounds on the base of germanium oxyethylendiphosphonate with nicotinic acid, nicotinamide and magnesium. – A manuscript. Thesis for a scientific degree of candidate of medical sciences in speciality 14.03.05 – pharmacology. – Odessa State Medical University Ministry of Health Care of Ukraine. – Odessa, 2008. – P.157.

 

19. Pat. 36684 Ukraine, (51) МПК (2008), А61К31/045, А61К33/00. Method of detoxication of organism at endotoxicosis of posttraumatic origin by means of coordination compound on the base of germanium, magnesium and oxyethylidenediphosphonic acid / V.D. Lukjanchuk, I.I. Seifullina, N. V. Risukhina, E.E. Martsinko. – Bull. №21. 10.11.2008.

 

20. Lukyanchuk V.D., Seifullina I.I., Risukhina N.V. EPR-spectrometric analysis of protective action of coordination compound of germanium with magnesium and oxyethylidendiphosphonic acid in conditions of crushsyndrome // J. Academy of Medical Sciences of Ukraine. – 2008. – Vol.14, No 3 – P. 593-601.

 

21. Pat. 613475А Ukraine, (19)UA, (51) МПК (2003), А61К31/455, А61К33/00. Coordination compounds of germanium with nicotinic acid having antihypoxant activity / I.I. Seifullina, V.D. Lukjanchuk, O.D. Nemyalyk. – Bull. №17.11.2003.

 

22. Pat. 22954 Ukraine, (19)UA, (51) МПК (2006), G01N 33/576, А61К 39/29. Method of pharmaceutical correction of toxic medicinal hepatitis / V.D. Lukjanchuk, M.A. Vnukova, I.I. Seifullina, O.O. Shpulina, V.N. Тkachenko. – Bull. №5. 25.04.2007.

 

23. Godovan V.V., Kresyun V.Y., Seifullina I.Y. Comparative Pharmacological Activity of New Biologically Active Substances — Derivatives of Diphosphonate Acids // Integrative Anthropology. International Medical and Philosophical Magazine. – 2007. – No. 2(10). – P. 13-17.

 

24. Seifullina I.I., Martsinko E.E., Spivak N. Ya., Zholobak N.M. The polymolecular aggregates of nicotinic acid, nicotinamide, pyracetam with oxyethylidenediphosphonatohydroxygermanium acid and their interferonogenic activities // Abstr. Rep. XX Ukr. Conf. Organic Chemistry. – Odessa, 2004. P. 443.

 

25. Pat. 66392 Ukraine, (51) МПК (2011.01), А61P 1/16 (2006.01), А61К 31/30 (2006.01), А61K 9/14 (2006.01). Medgerm as biologically active hepatoprotective agent / O.L. Tymchishin, V.V. Godovan, V.Y. Kresyun, I.I. Seifullina, E.E. Martsinko. – Bull. №24. 26.11.2011.

 

26. Pat. 20555 Ukraine, (19)UA, (51) МПК (2006), А61К 35/30. The method of pharmacological correction of a craniocereberal trauma / Lukyanchuk V.D., Seyfullina І.I., Vysotsky A.A., Martsinko E.E., Pesaroglo O.G. – Bull. №1. 15.01.2007.

 

27. Pat. 71812 Ukraine, МПК (2012.01) А61Р 9/00 А61К 33/00. Potassium bis(citrato)germanate (IV) that shows the antiischemic activity / V.D. Lukyanchuk, І.O. Zhitina, I.I. Seifullina, E.E. Martsinko. – Bull. № 14.





DOI: https://doi.org/10.18524/2304-0947.2015.4(56).56690

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