Авторы

  • M G’oyibnazarova
    Tashkent Pharmaceutical Institute
  • G Pulatova
    Tashkent Pharmaceutical Institute
  • M Fatxullayeva
    Tashkent Pharmaceutical Institute
  • F Jumabaev
    Tashkent Pharmaceutical Institute

DOI:

https://doi.org/10.71337/inlibrary.uz.ejar.138013

Аннотация

Glutaric acid (pentanedioic acid) is an aliphatic organic compound used as a raw material in the synthesis of anticancer drugs and antibiotics, pharmaceutical and chemical products, as well as a model compound for understanding metabolic disorders and hereditary enzyme deficiencies. Cobalt, being a component of vitamin B12, forms complexes, and its deficiency leads to anemia. Therefore, the synthesis of a complex compound involving glutaric acid, nicotinamide, and cobalt, followed by an analysis of its physicochemical and pharmacokinetic properties, is an important research task.

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401

Volume 5, Issue 10: Special Issue
(EJAR)

ISSN: 2181-2020

MPHAPP

THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE

MODERN PHARMACEUTICS: ACTUAL

PROBLEMS AND PROSPECTS

TASHKENT, OCTOBER 17, 2025

in-academy.uz

MIXED-LIGAND COMPLEX OF COBALT WITH GLUTARIC ACID AND

NICOTINAMIDE (CoGANA) MOLECULAR DOCKING ANALYSIS

G’oyibnazarova M.A.

Pulatova G.U.

Fatxullayeva M.

Jumabaev F.R.

Tashkent Pharmaceutical Institute, Uzbekistan

e-mail: g.u.pulatova.@mail.ru, phone: +99894-695-52-25

https://doi.org/10.5281/zenodo.17340327

Relevance:

Glutaric acid (pentanedioic acid) is an aliphatic organic compound used as a raw

material in the synthesis of anticancer drugs and antibiotics, pharmaceutical and chemical products,
as well as a model compound for understanding metabolic disorders and hereditary enzyme
deficiencies. Cobalt, being a component of vitamin B12, forms complexes, and its deficiency leads
to anemia. Therefore, the synthesis of a complex compound involving glutaric acid, nicotinamide,
and cobalt, followed by an analysis of its physicochemical and pharmacokinetic properties, is an
important research task.

Objective of the study:

To determine, from the perspective of energy efficiency, the most

stable conformations of the mixed-ligand cobalt complex with glutaric acid and nicotinamide
(CoGANA) when interacting with target proteins.

Materials and methods:

The molecular docking analysis of the CoGANA molecule was

carried out using Biovia DS Visualizer software and the CB-Dock 2 web server.

Results and discussion:

Molecular docking is one of the main in silico research methods,

enabling the development of new and effective drugs. At the beginning of our study, protein structures
with the following PDB ID numbers: 1SCZ, 3WD0, 4LEP, 5RVW, 5RVX, 5RVY, 5RVZ, 5RVW1,
5RVW0, and 6SV1 were downloaded in .pdb format from the Protein Data Bank (PDB)
(

https://www.rcsb.org/

). Afterward, the binding efficiency of CoGANA with these proteins and the

formation of stable conformations were determined. For this, water molecules and heteroatoms,
particularly existing ligands, were removed from the protein structures using Biovia DS Visualizer,
cleaned, and saved in .pdb format for further stages [1]. The cleaned proteins were then subjected to
docking analysis via the CB-Dock 2 web server [2]. This server automatically identifies the active
site of proteins and provides the binding energy of the top 5 conformations between CoGANA and
the protein. According to the results, the 5RVW0 protein exhibited the lowest binding energy (BE)
with the complex, -7.2 kJ/mol, while 5RVZ and 5RVX proteins showed the highest binding energies,
-9.9 and -10.4 kJ/mol, respectively. The CoGANA complex formed two hydrogen bonds with the
carboxyl group involving SER A:288 (2.40Å) and LEU A:368 (2.82Å), and two hydrogen bonds with
the amino group involving GLN B:664 (2.18Å) and GLN B:594 (2.15Å) in 5RVX. In addition,
hydrogen bonding occurred with TYR A:190 (3.17Å) and LEU A:290 (3.09Å) through the nitrogen
atom in the ring structure. ASN A:286 (3.28Å), SER A:335 (2.79Å), and ALA A:334 (3.24Å) also
formed hydrogen bonds with the carboxyl group of the complex. For 5RVZ, HIS A:223 (3.12Å),
LYS A:188 (3.04Å), and TYR A:190 (3.29Å) residues bonded with the oxygen atom of CoGANA’s
carboxyl group; THR B:600 (2.17Å) bonded via the hydrogen atom of the carboxyl group; and SER
A:288 (1.77Å) bonded through the hydrogen atom of the amino group.

Conclusion:

For the first time, the molecular docking analysis of the cobalt complex with

glutaric acid and nicotinamide (CoGANA) was performed. The results showed that the 5RVZ and


background image

402

Volume 5, Issue 10: Special Issue
(EJAR)

ISSN: 2181-2020

MPHAPP

THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE

MODERN PHARMACEUTICS: ACTUAL

PROBLEMS AND PROSPECTS

TASHKENT, OCTOBER 17, 2025

in-academy.uz

5RVX proteins exhibited the highest binding energies with CoGANA, -9.9 and -10.4 kJ/mol,
respectively. This indicates that the binding energy of the ligand molecule (glutaric acid) with these
proteins, -5.5 and -5.4 kJ/mol, is 80–93% lower. These results, of course, require further validation
through in vivo and in vitro studies.