No abstract

The first example of molecular docking of the SARS-CoV-2 main protease for COVID-19 [Mpro, Protein Data Bank (PDB) code 7BQY] by a chalcone-based ligand, namely, (E)-1-(2,4-dichlorophenyl)-3-[4-(morpholin-4-yl)phenyl]prop-2-en-1-one, C19H17Cl2NO2, I, is presented. Two-dimensional (2D) LIGPLOT representations calculated for the inhibitor N3, viz. N-{[(5-methylisoxazol-3-yl)carbonyl]alanyl}-L-valyl-N 1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide, and 7BQY are included for comparison with our chalcone-based complexes. The binding affinity of our chalcone ligand with 7BQY is −7.0 kcal mol−1, a high value which was attributed to the presence of a hydrogen bond, together with many hydrophobic interactions between the drug and the active amino acid residues of the receptor. Docking studies were also performed, employing rigid and flexible binding modes for the ligand. The superposition of N3 and the chalcone docked into the binding pocket of 7BQY is also presented. The synthesis, single-crystal structure, Hirshfeld surface analysis (HSA) and spectral characterization of heterocyclic chalcone-based compound I, are also presented. The molecules are stacked, with normal π–π interactions, in the crystal.

A series of tetracarboxamide Schiff base and macrocyclic pentaazapyridines has been prepared from 3,5-bis(N-(1-hydrazinyl-1-oxo-3-phenylpropan-2-yl))pyridine carboxamide 4 as starting material, which was synthesized from 3,5-dinicotinic acid 1. Treatment of 4 with 1,4-diaminobutane, 1,6-diaminohexane or cycloalkanone derivatives gave the corresponding macrocyclic tetracarboxamides 5a and 5b, and cycloalkyl Schiff bases 6a-6c, respectively. Treatment of 4 with acetophenone or acetylpyridine derivatives gave the corresponding Schiff bases 7a-7e and 8a-8c, respectively. Carboxylic acid hydrazide 4 was treated with acid anhydrides in glacial acetic acid to afford the corresponding diimide tetracarboxamides 9-11, respectively. The structures of newly synthesized compounds are established by physical and spectral data evidences. Some of the synthesized compounds were screened as antimicrobial agents.

(3-(4-bromophenyl)oxiran-2-yl)(2,4-dichlorophenyl)methanone 2 was synthesized via treating of 3-(4-bromophenyl)-1-(2,4-dichlorophenyl) prop-2-en-1-one 1 with hydrogen peroxide in the presence of sodium hydroxide in a mixture from acetone and methanol with stirring. The structure and purity of the synthesized product was confirmed by elemental analysis, IR, nuclear magnetic resonance (1H NMR and 13C NMR), mass spectroscopy and X-ray single crystal. The obtained compound 2 was screened as antimicrobial activity compared to Streptomycin and Fusidic acid as reference drugs.