In silico study of new bis-3R, 4R′-5-(((1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thione derivatives
DOI:
https://doi.org/10.14739/2409-2932.2019.3.184186Keywords:
triazoles, synthesis, molecular docking simulations, virtual screeningAbstract
A combination of two rings of 1,2,4-triazole with the formation of new hybrids, bis-1,2,4-triazoles, with various functional groups and pharmacophores may comprise a promising class of the biologically active compounds. Alkaline phosphatases belong to a broad family of enzymes, ectonucleotidases, which are responsible for the dephosphorylation of nucleoside phosphates and have an impact on the metabolic processes in the organism.
The purpose of this work was to conduct virtual screening and molecular docking of the initial 4-alkyl-5-(((3-(pyridine-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiols, which are promising bioactive compounds capable of inhibiting alkaline phosphatase.
Materials and methods. All compounds were synthesized by the general method. Virtual screening was held using PASS software. Molecular docking research was done using Autodock 4.2.6 software. The screening was held on the crystallographic structure of the “EC 3.1.3.1 Alkaline phosphatase” (1SHN) enzyme.
Results. The analysis of the computer-based prognosis demonstrated that the research of the inhibition of alkaline phosphatase, histininkinase, nucleotide and phosphatase metabolism, diuretic and antineoplastic properties among these compounds is relevant. The compounds exhibit a wide array of biological activities, among which the inhibition of alkaline phosphatase and antitumor activity are the most immediate. Molecular docking was showed that the compounds had a high affinity to the “EC 3.1.3.1 Alkaline phosphatase” (1SHN) enzyme, specifically -7.08 kcal/mol and -7.88 kcal/mol, respectively. It was established that Carbon atoms at the 4-position of 1,2,4-triazole reacted with water molecules (using hydrogen bond) and the amino acid residue of the THR B:435. The Carbon was acted as an electron donor in the hydrogen bond with the relation of -Alkyl to THR B:435 (2.11 Å). According to this research, this structural modification of 1,2,4-triazole is promising.
Conclusions. The data of computer prognosis show promise the search of bioregulators among the studied compounds on two promising directions: alkaline phosphatase inhibition and antineoplastic activity. Molecular docking was showed the high affinity of the selected compounds to the “EC 3.1.3.1 Alkaline phosphatase” (1SHN) enzyme, which may be present due to water molecules (using hydrogen bond) and the amino acid residue of the threonine, high number of hydrophobic bonds, negatively and positively charged particles, and polar bonds.
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