Abstract
In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.
Highlights
Infective diseases have become one of the most serious threats to global health due to appearance and expansion of microorganisms’ resistance to a majority of therapeutics currently utilized for their treatment (Abo-Bakr et al, 2021)
Infrared spectra (IR) spectrum revealed the presence of carbonyl group at 1,665 cm−1.1H-NMR spectrum showed signals assigned for thiol group protons, aromatic protons, and C-H proton
Its IR spectrum revealed the disappearance of the carbonyl group band and the appearance of a peak characteristic for C S at 1,143 cm−1
Summary
Infective diseases have become one of the most serious threats to global health due to appearance and expansion of microorganisms’ resistance to a majority of therapeutics currently utilized for their treatment (Abo-Bakr et al, 2021). Heterocyclic cores are versatile privileged scaffolds present in many biologically active molecules (Welsch et al, 2010) and pharmaceuticals (Balaban et al, 2004; Kowada et al, 2010). The ketene gem-dithiols act as 1,3-electrophilic synthons besides the activity role as building blocks in the synthesis of cyclic molecules. Oxoketene gem-dithiols are important multifunctional substrates for the synthesis of heterocyclic compounds, in addition to the nematicidal and bactericide properties (Zayed, 1996, 2007; Liang et al, 2014; Hassan et al, 2020)
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