Organizing co mmittee

DITERPENOID ALKALOIDS OF THE ACONITUM PLANTS OF
KYRGYZSTAN 
 
U.T. Teshebaeva
1
, Z.S. Boronova
1
, M.N. Sultankhodzhaev
2
,
 
F.N.Dzhakhangirov
2 
. 
1.
 
Osh State University, Osh, Republic Kyrgyzstan. 
2.
 
S.Y.Yunusov Institute of Chemistry of Plant Substances, AS Republic
Uzbekistan. Uzbekistan, Tashkent 700 170, Mirzo Ylugbek Str. 77. 
On the territory of Kyrgyzstan grow 9 kinds of Aconitum plants. We have studied 
alkaloidal constituents of Aconitum zoongaricum Stapf. and Aconitum karakolicum 
Rapaics, which were used in folk medicine for treatment rheumatism, migraines and 
toothache. 
From the roots of
Aconitum soongaricum Stapf
. we have isolated several known and 
knew alkaloids such as aconitine, aconifine, flaconitine, napelline, napelline N-oxide, 
neoline, songorine, 12-acetylnapelline, 15-asetulsongorine, acozonine and acozonitine. 
From the roots of
Aconitum karakolicum Rapaics
, we have isolated alkaloids
karakoline,12-acetylnapelline,1-benzoilkarasamine,delsoline,dehydrosongorine, 
karakanine, karakolidine, montikamine. 
Fharmakological study of above listed alkaloids show the cardiotoxic, analgetic, 
local anaesthetic, antiinflammatory and antitoxic to aconitine activity.
 

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Oral presentation
29 
In silico STUDY OF BUFADIENOLIDES 
FROM Bufo viridis VENOM 
 
M.B. Kayumov, Z.Zh. Mirakhmetova, N.R. Mukhamedov, Sh.Ya. Mirzaakhmedov 
Institute of Bioorganic Chemistry, 100125, Tashkent, Mirzo Ulugbek street 83 
e mail: [e-mail] 
In recent years, there has been increasing attention to study active substances isolated 
from the natural origin which are effectively inhibited Sars-Cov-2. The main protease 
(M-pro) of Sars-Cov-2 is one of the perfect targets to combat against the virus. Last 
three years there has been demonstrated several synthetic drugs which can inhibit M-
pro. Bufadienolides from toad venoms has anti-cancer, anti-bacterial, anti-arrhythmic 
and anti-viral activities. Therefore, in-depth physicochemical and pharmaco-biological 
evaluation of bufadienolides is of great interest. Besides, bufadienolides including 
bufalin, arenobufagin, marinobufagin, telocinobufagin, bufarenogin, gamabufotalin 
extracted from Central Asian green toad, 
Bufo viridis 
venom still in demand of deeper 
investigation as an anti-Sars-Cov-2 compound. In this work, we presented 
in silico
analysis of 6 bufadienolides from toad 
Bufo viridis
venom applying molecular docking 
and molecular dynamics studies to study the possible receptor-ligand complex binding 
types and structural integrity of the complex. For free energy calculation, we used an 
umbrella sampling simulation. 
For docking analysis used MOE 2014.0901 software and 3D structures of 
bufadienolides obtained from PubChem database in SDF and MOL format. The x-ray 
structure of 3CL protease (PDB ID: 7KPH) was downloaded from RCSB Protein Data 
Bank and protein was prepared using the software default Structure Preparation 
application. MD simulation carries out by GROMACS-2020 software package applying 
the CHARMM27 all-atom force field. To check the stability, of the protein-ligand 
complex, we calculated the root mean square deviation (RMSD), and root mean square 
fluctuations (RMSF). The final frame of the complex was extracted for umbrella 
sampling (US) simulation. The complex was enclosed in an appropriately sized box, 
and the centre of mass of the ligand was then pulled along the y-axis by applying an 
external force, while the protein was restrained and served as a reference for tension 
modelling. In the pulling simulation, a spring constant of 1000 kJ/(mol*nm
2
) and 
pulling at a rate of 0.01 nm/ps for 500 ps were used. We identified 50 umbrella 
windows each 0.1nm then windows stabilized for 100 ps and then a 10 ns US 
simulation was performed. Among ligands the gamabufatalin in complex with 3CL-
protease presented short equilibration time (5ns) at the 0.25-0.75 A
o
with low range of 
RMSD value around 0.5 A
o
. Reduced RMSF tones were obtained at residues 40-56, 
130-150 and 180-190 of the active sites due to the interaction of the ligand with pocket 
amino acids. The free energy profile in the US simulation was calculated as -49.8 
kJ/mol for the ligand-protein, indicating the formation of the most stable complex.MD 
and US simulation data analysis results exhibited that, the gamabufatalin might be an 
effective inhibitor against to SARS-Cov-2 main protease. Nowadays detailed 
in-vitro
analysis of bufadienolides are going on. 

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Oral presentation 
30