Биологические науки/ 9. Биохимия и биофизика

MD Rasulov M.M., ChD Storozhenko P.A., a student Susova M.I.,

post-graduate Rasulov R.M.

State Research Institute for Chemistry and Technology

of Organoelement Compounds, Moscow

ADAPTOGEN DEVELOPMENT CONCEPT AND

PATHOLOGICAL STATE CORRECTION

Revolutionary discoveries in recent years, registered in the field of molecular biology and genetics, forced to reconsider previous concepts regarding both the normal functioning of the body, and the formation of pathological processes. This, in turn, opens up new horizons for the preparation of the drugs aimed at correction of pathological states..In this regard the evolution of adaptogen synthesis concept is of interest.

In 1937 Irvine discovered the possibility to synthesize hypervalent compounds of some metals. This discovery formed the basis for the development of biologically active silicon compounds that had been considered inert. The discovery made by M.G. Voronkov of high specific biological activity of sulatranes – RSi(CH₂CH₂)_n and this microelement role in vital processes [1, 2] initiated the development of a new branch of silicon chemistry – bioorganosilicon chemistry. Within the framework of this branch we were engaged in developing “Sila-Pharmaka” trend. Silatranes were found to promote protein and nucleic acids synthesis, facilitate proliferative-reparative function of the connective tissue, accelerate the healing of wounds and burns, produce anti-stress and adaptogenic effect [3, 4].

In 1968 1-(organyle) germatranes – RGe(OCH₂CH₂)₃ N were synthesized for the first time and the study of their biological activity started. Biological activity of germatranes is being currently investigated and prepared for practical use [5]. It gave us the basis to define a new trend – «farmeos», or « pharmacology of organoelement compounds». It should be mentioned that hypervalent zinc compounds RZn(CH₂CH₂)_n or zincatranes have been synthesized recently and their biological activity is successfully studied [6, 7]. Considering that both metals and metalloids may serve as a radical in atranes formula, we should extent the understanding of research trends in hypervalent triethanolamine derivatives spectrum that is not covered by the definition «sila- or germapharmaca».

Specific kinases, AMP activated protein kinases (AMPK) - cellular energy sensors, are one of the major targets experiencing the effect of stimulants. Epigenetic control mechanisms of key units of cascade reactions caused by natural stimulants remain undiscovered. The suppression of inefficient energy use processes by AMPK simultaneously with the observed mimetic and neuroprotective effects of polyphenols and resveratrol suggests that natural stimulant effect occurs through these kinases. Resveratrol was found to activate AMPK in brain cells and tissue. We have found that resveratrol through AMPK stimulates mitochondria biogenesis as well. These data prove the existence of common mechanisms in metabolism activators effect through the energy metabolism improvement or/and mitochondria biogenesis promotion. Within the frame work of the school “theta pharma” which is being developed by our team we plan to investigate molecular mechanisms of new domestic adaptogen action through gene expression evaluation that has been confirmed from the viewpoint of their key role in mitochondria biogenesis.

Such is the evolution of the doctrine of the development of a new adaptogen generation and study of their biological activity.

References:

1. Rasulov M.M., Voronkov M.G. Organoelement compounds for medications: yesterday, today and tomorrow // Vestnik RAEN, 2008, V.8., No 1, P.82-86.

2. Rasulov M.M.., Nurbekov M.K., Susova M.I. Aminoacyl-tRNA-synthetase participation in physiological processes control in health and disease // In: Herbal medicine and folk medicine of Avicenna era. Dushanbe, 2010, p.314-316

3. Voronkov M.G., Adamovich S.N., Mirskov R.G., Mirskova A.N. Synthesis of new biologically active O-hydridemetalloatranes // Zhurnal Obshchei Khimii, 2009, v.79, No 1, p.162-163.

4. Voronkov M. G., Nurbekov M. K. Rasulov M.M., Zvereva M. V., Mirskova A. N., R. G. Mirskov Adamovich S. N. The Complex of Zinc bis-(2- Methylphenoxyacetate) with Tris -2 (hydroxyl-ethyl) Amine as an Activator of Synthesis of Total Tryptophanyl -tRNA Synthetase. // Doklady Biochemistry and Biophysics, 2012, Vol. 444, pp. 147–148.

5. Voronkov M.G., Storozhenko P.A., Rasulov M.M. Biochemical analysis of hepatoprotective activity of tris (2-oxy-ethyl ammonium ) orthocresoxyacetate and 1-hydroxygermatrane // Entsiclopediya inzhenera-khimika 2013, No 9, p.8-12

6. Voronkov M.G., Yushkov G.G., Mashanov A.V., Fedorin A.Yu., Rasulov M.M., Benemanskii V.V. Zitramin —a new antidote of acute ethanol intoxication // Doklady Akademii Nauk, 2013, v.451, No 6, p.646-648.

7. Rasulov M. M., Voronkov M. G., Storozhenko P.A., Sakharovskaya G.B.

Atranes – a new generation of biologically active substances used in medicine and agriculture // Entsiclopediya inzhenera-khimika 2013, No 12, p.7-18