APPLICATION OF MATHEMATICAL MODELING AND PHYSICO-CHEMICAL ANALYSIS METHODS IN THE PREDICTION OF BIOLOGICAL ACTIVITY AND QUALITY CONTROL OF GOSSYPOL DERIVATIVES

ELENA V. USPENSKAYA; POLYNA А. ZABORKINA; EVGENIYA A. RYNDINA; TATYANA V. PLETENEVA; MARIYA A. MOROZOVA; ILAHA V. KAZIMOVA; ANTON V. SYROESHKIN

doi:10.22159/ijap.2022v14i6.46052

Authors

ELENA V. USPENSKAYA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation https://orcid.org/0000-0003-2147-8348
POLYNA А. ZABORKINA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation https://orcid.org/0000-0001-8832-7603
EVGENIYA A. RYNDINA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation https://orcid.org/0000-0003-4023-682X
TATYANA V. PLETENEVA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation https://orcid.org/0000-0001-7297-980X
MARIYA A. MOROZOVA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation https://orcid.org/0000-0003-1586-2183
ILAHA V. KAZIMOVA Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
ANTON V. SYROESHKIN Department of Pharmaceutical and Toxicological Chemistry, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St, Moscow, 117198, Russian Federation

DOI:

https://doi.org/10.22159/ijap.2022v14i6.46052

Keywords:

Gossypol-acetic acid, In silico methods, Pa/Pi ratios, Quality control, Analysis of physical and chemical properties

Abstract

Objective: The purpose of this work was to evaluate in silico biological activity profiles of real and virtual molecular structures of gossypol derivatives and to develop methods of Physico-chemical analysis to control their quality.

Methods: Substance of gossypol-acetic acid (GAA) and 14 virtual derivatives; PASS and ChemicDescript QSAR methods; low angle and dynamic laser light scattering (LALLS, DLS) methods; IR Spectroscopy–Cary 630 Fourier Transform IR Spectrometer, UV spectrometry–Cary-60 spectrophotometer, Optical microscopy (Altami BIO 2 microscope); Spirotox method for a sample’s biological activity.

Results: A distance-based topological Balaban index (J) was successfully selected by ChemicDescript analysis; the P_a meaning by PASS Online program showed maximum (from 0.8 to 0.9) variations of antitumor and antiandrogenic and minimum of antiviral activities of GAA derivatives (P_a<0.5) despite the existing literature data. Microscopy and DLS methods demonstrated the values of high powder dispersion d=0.8 nm and weak stability of colloidal particles =-0.9 mV. According to UV data =42.4±0.8 (100 ml·g^-1·cm^-1) at λ_max=380 nm. The LALLS method determined the GAA dissolution rate constant in ethanol: k=0.041±0.004 s^-1. The calculated activation energy values of cell biosensor death process in 1 mmol solution of GAA in N,N-DMF: °^bsE_a=174.36±0.45 kJ·mol^-1 in comparison with the solvent medium: °^bsE_a=213±1.55 kJ·mol^-1

Conclusion: The developed approach of chemometric, laser and biotesting methods can be used for the identification of biologically active properties, as well as for qualitative analysis within the development of the standard for the pharmaceutical substance of natural polyphenols.

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