Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Abstract

Tetrazoles are conjugated nitrogen-rich heterocycles considered as bio-isosteres of carboxylic acids. Tetrazoles owing to their conjugated structures serve as biologically relevant potent scaffolds. The present research paper reports the successful synthesis and single crystal analysis of three different tetrazole derivatives (2, 4, 6). The synthesized tetrazole derivatives were evaluated for their possible cytotoxicity LD50 (52.89, 49.33, 17.28 μg/ml) and antileishmanial activities IC50 (0.166, 10, 5.0 μg/ml). Moreover, molecular docking studies were performed to determine the possible interaction sites of the tetrazole derivatives (2, 4, 6) with TryR, an enzyme involved in the redox metabolism of the Leishmania parasite. Docking computations demonstrates that the tetrazole derivatives (2, 4, 6) established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. The results suggested that the synthesized tetrazole derivative (2, 4, 6) can be possible hit candidates which can be tested further against amastigote stage of parasite and then in an animal model of leishmaniasis.

Estrogenic Activity of Tetrazole Derivatives Bearing Bisphenol Structures: Computational Studies, Synthesis, and In Vitro Assessment

“…A. Bladin, is a high nitrogen-containing heterocycle with four nitrogens and a carbon atom. It is planar, and its negative charges can be delocalized over five ring atoms, resulting in a reduced per atom charge, 21 thus favoring receptor−ligand interactions or hindering the interactions as a consequence of the interfacial charge density. To date, receptor−ligand interactions and studies to determine the estrogenicity or nonestrogenicity of tetrazole derivatives bearing bisphenol have not been reported.…”

Insights into the actions of angiotensin-1 receptor (AT1R) inverse agonists: Perspectives and implications in COVID-19 treatment

“…The presence of amide and ester groups in ARB drugs are responsible for their high affinity for the AT1R, and the effects they produce. Tetrazolate anions (nitrogen-rich five-membered heterocycles, a common pharmacophoric group of some ARB drugs) are more lipophilic than carboxylates, which promotes the passage of drug molecules through cell membranes, and makes them more resistant to metabolic degradation pathways, with a longer duration of action (Aziz et al, 2018[ 7 ]). The tetrazolate pharmacophoric group is common in AT1 inverse agonists (tetrazole ARB drugs) and the binding of the tetrazole moiety with the AT1R involves multiple binding through contact with residues of lysine and histamine that constitute the same subsite of the ligand binding pocket (Noda et al, 1995[ 86 ]).…”

DFT Study on Corrosion Inhibition by Tetrazole Derivatives: Investigation of the Substitution Effect

“… 16 Also, while tetrazole rings are weak bases, by having a proton connected to the N1 or N2 position, they show strong acidic character in the range of carboxylic acids (p K a ∼ 4.75). 17 − 19 Moreover, tetrazole derivatives are aromatic, and the structural parameters are considerably affected by the quiddity of the substituent in the ring. 20 − 22 …”

“…Generally, tetrazoles exist in two tautomeric forms (1 H and 2 H , see Scheme ), in which the 2 H -form prevails in the gas phase, while the 1 H -form is more stable in the liquid . Also, while tetrazole rings are weak bases, by having a proton connected to the N1 or N2 position, they show strong acidic character in the range of carboxylic acids (p K a ∼ 4.75). − Moreover, tetrazole derivatives are aromatic, and the structural parameters are considerably affected by the quiddity of the substituent in the ring. − …”