Synthesis of antimicrobial azoloazines and molecular docking for inhibiting COVID-19

Abstract

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds 4, 5, 17a,b, 19, and 25 against the pathogenic fungal strains used; Aspergillus flavus and Candida albicans compared to ketoconazole. In addition, compounds 4, 5, 19, and 25 showed moderate antibacterial activities against most tested bacterial strains. Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of Candida albicans, suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.

SCHEME 1

Synthesis of hydrazonoyl chlorides 4 and 5 [Colour figure can be viewed at wileyonlinelibrary.com]

SCHEME 2

Synthesis of triazolopyrimidines 9a,b [Colour figure can be viewed at wileyonlinelibrary.com]

SCHEME 3

Synthesis of triazolopyrimidine derivatives 13a‐d [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 1

The ¹H NMR of compound 13b [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

The ¹³C NMR of compound 13d [Colour figure can be viewed at wileyonlinelibrary.com]

SCHEME 4

Synthesis of triazoloperimidine derivatives 17a,b [Colour figure can be viewed at wileyonlinelibrary.com]

SCHEME 5

Reaction of hydrazonoyl chloride 5 with 1,8‐diaminonaphthalene 18 and perimidine derivatives 20a,b [Colour figure can be viewed at wileyonlinelibrary.com]

SCHEME 6

Reaction of hydrazonoyl chlorides 4 and 5 with 4‐amino‐5‐trifluoromethyl‐4H‐[1,2,4]triazole‐3‐thiol 22 [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

The 2D and 3D proposed binding modes of 4 docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

The 2D and 3D proposed binding modes of 5 docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

The 2D and 3D proposed binding modes of 17a docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

The 2D and 3D proposed binding modes of 17b docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 7

The 2D and 3D proposed binding modes of 19 docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 8

The 2D and 3D proposed binding modes of 25 docked in the active site of Candida albicans leucyl‐tRNA synthetase [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 9

The 2D and 3D proposed binding modes of 4 docked in the active site of COVID‐19 3CLpro [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 10

The 2D and 3D proposed binding modes of 5 docked in the active site of COVID‐19 3CLpro [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 11

The 2D and 3D proposed binding modes of 13c docked in the active site of COVID‐19 3CLpro [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 12

The 2D and 3D proposed binding modes of 13d docked in the active site of COVID‐19 3CLpro [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 13

The 2D and 3D proposed binding modes of 25 docked in the active site of COVID‐19 3CLpro [Colour figure can be viewed at wileyonlinelibrary.com]