Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

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.

Insight into Indole‐Based Heterocyclic Scaffolds: A Medicinal Chemistry Perspective

“…Entesar A. Hassan et al [21] . developed a novel method for the synthesis of indole‐based furan derivatives (9) by reacting the compound (7) and succinyl dichloride (8) in 2 : 1 M ratio in boiling THF solvent and Et 3 N catalyst under refluxing for 5 h.…”

تحوير وتشخيص بعض مشتقات الليفوفلوكساسين الحلقية غير المتجانسة كمثبطات إنزيم Cox-2 وتقييم فاعليتها الحركية الدوائية عن طريق الالتحام الجزيئي ودراسات Adme السويسرية.

“…Physical characteristics, 1 H-NMR, 13 C-NMR, FT-IR spectroscopy, and other methods were used to characterize and identify the produced compounds. The newly created compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) were based in part on the well-known antiinflammatory medication levofloxacin. The Swiss ADME server was used to perform computational techniques, such as ADME studies, in order to forecast the pharmacokinetics of the novel drugs.…”

“…The Swiss ADME server was used to perform computational techniques, such as ADME studies, in order to forecast the pharmacokinetics of the novel drugs. To assess the selectivity of created compounds towards the COX-2 enzyme, the results showed that all compounds met the Lipinski rule of five compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Higher PLP fitness values than the reference compound are predicted by docking studies for ligand interactions with COX-2 protein to bind with amino acids in the active pocket (Levofloxacin ).…”

“…various biological disciplines because of their activity in various diseases 3 . It has been used to create pharmaceuticals that are anticancer, antifungal, anti-viral, antioxidants, anti-microbial, and antibacterial 4,5 . In the development of novel energetic molecules.…”

In silico study to identify novel potential thiadiazole-based molecules as anti-Covid-19 candidates by hierarchical virtual screening and molecular dynamics simulations

“…Urgent needs for develoment novel anti-Covid19 agents have directed us to synthesize some new bioactive heterocyclic molecules. In the present study, we aimed to identify potential Covid-19 inhibitors through a computer-based molecular docking and molecular dynamics techniques [14][15][16]. In addition, ADMET (absorption, distribution, metabolic, excretion, and toxicity) and pharmacokinetics parameters of the prepared ligand molecules were performed to identify their drug-likeness properties [17].…”